Journal of Inherited Metabolic Disease via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Journal of Inherited Metabolic Disease' source. Sun, 21 Mar 2010 16:41:18 +0100 Fatal cerebral edema associated with serine deficiency in CSF http://www.medworm.com/index.php?rid=3386679&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb522r0596x173235%2F Abstract  Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3386679 Thu, 18 Mar 2010 19:38:43 +0100 3386679 Large neutral amino acids in daily practice http://www.medworm.com/index.php?rid=3386680&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3748x52775308584%2F Abstract  At the Kennedy Centre for Phenylketonuria, Denmark, large neutral amino acids (LNAAs) are being used to treat adult and adolescent patients who are nonadherent to dietary treatment for phenylketonuria (PKU). At the start of treatment, a patient must undergo dietary analysis and regular blood sampling to measure plasma amino acid (AA) concentrations. The aim of this analysis and treatment is that the patient receives 25–30% of the daily protein requirement from LNAA supplementation and the remaining 70–75% from natural, low-phenylalanine proteins (although some patients have difficulties in maintaining this level of protein intake). Patients are therefore able to follow a more “normal” diet than those adhering to a PKU diet with AA supplementation (in which... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3386680 Thu, 18 Mar 2010 19:38:37 +0100 3386680 Hydroxocobalamin for cobalamin C: which dosage? http://www.medworm.com/index.php?rid=3361710&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw580044x26306425%2F Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s10545-010-9068-8Authors Viroj Wiwanitkit, Wiwanitkit House 38/167 Sukhapibarn 1 Road Bangkhae, Bangkok Thailand 10160 Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3361710 Thu, 11 Mar 2010 18:25:13 +0100 3361710 Profound biotinidase deficiency: a rare disease among native Swedes http://www.medworm.com/index.php?rid=3361711&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv2616k6533r72v6j%2F Abstract  Biotinidase deficiency is an autosomal recessive metabolic disorder included in many newborn screening programmes. Prior to the introduction of screening for biotinidase deficiency in Sweden in 2002, the disorder was almost unknown, with only one case diagnosed clinically. Biotinidase activity was measured in dried blood spots with a semiquantitative method using biotin-6-amidoquinoline as substrate. The cutoff value was set at 25% (later lowered to 20%) of the mean activity of all samples measured on that day. The disorder was confirmed by quantitative determination of biotinidase activity in plasma and DNA analyses. Over a period of 6 years, 13 patients were identified among 637,452 screened newborns and 5,068 adoptive/immigrant children. None of the patients ha... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3361711 Thu, 11 Mar 2010 18:25:10 +0100 3361711 Long-term follow-up of patients with phenylketonuria receiving tetrahydrobiopterin treatment http://www.medworm.com/index.php?rid=3361714&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F733m025x2pk8l3kv%2F Abstract  Treatment with tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH4-responsive phenylketonuria (PKU). A number of studies has reported on the short-term BH4 treatment of patients with PKU, but long-term data are lacking. Here, we describe the effects of long-term treatment with BH4 on 16 patients, who showed a >28% reduction in blood Phe following testing for BH4 overload. The mean dose of BH4 was 16 mg/kg body weight (range 5–36 mg/kg body weight). The mean treatment duration was 56 months (range 24–110 months). Of 16 patients, 14 achieved long-term Phe control with BH4 treatment, with a mean blood Phe concentration of 321 ± 236 µmol/l. T... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3361714 Wed, 10 Mar 2010 18:33:33 +0100 3361714 Docosahexaenoic acid status in females of reproductive age with maple syrup urine disease http://www.medworm.com/index.php?rid=3361713&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F714l13j3w7516k63%2F Abstract  Individuals with maple syrup urine disease (MSUD) have impaired metabolism of branched-chain amino acids (BCAA) valine, isoleucine, and leucine. Life-long dietary therapy is recommended to restrict BCAA intake and thus prevent poor neurological outcomes and death. To maintain adequate nutritional status, the majority of protein and nutrients are derived from synthetic BCAA-free medical foods with variable fatty acid content. Given the restrictive diet and the importance of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in neurological development, this study evaluated the dietary and fatty acid status of females of reproductive age with MSUD attending a metabolic camp. Healthy controls of similar age and sex were selected from existing normal labora... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3361713 Wed, 10 Mar 2010 18:33:33 +0100 3361713 Efficacy of recombinant human α-L-iduronidase (laronidase) on restricted range of motion of upper extremities in mucopolysaccharidosis type I patients http://www.medworm.com/index.php?rid=3361712&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp311p5126t2w9257%2F Abstract  The aims of the study were to assess the effectiveness of enzyme replacement therapy (ERT) with laronidase on the range of motion (ROM) of upper extremities and influence on activities of daily living (ADLs) of patients with mucopolysaccharidosis type I (MPS I). The ROM of 17 patients with MPS I was followed from the first year of life until the introduction of ERT and after 52–208 weeks of treatment. In all patients (group 1, n = 10), passive ROM was assessed. In patients with Hurler/Scheie or Scheie phenotype (group 2, n = 7) both passive and active ROM, as well as daily life activities, were evaluated. Passive and active ROM was measured by a goniometer, while a health assessment questionnaire was used to assess activities ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3361712 Wed, 10 Mar 2010 18:33:33 +0100 3361712 Newborn screening strategies for congenital hypothyroidism: an update http://www.medworm.com/index.php?rid=3330321&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn0t223124774389v%2F Abstract  It is the purpose of this article to briefly review the initial development and subsequent evolution of newborn screening programs to detect infants with congenital hypothyroidism (CH) and then to provide an update of the advantages and disadvantages of the main test strategies. Pilot programs began screening newborn populations in North America in the mid-1970s using either primary thyroxine (T4)-follow-up thyroid stimulating hormone (TSH) or primary TSH testing. Many programs in the United States and around the world continue to prefer a primary T4-follow-up TSH test strategy. This approach has the advantage of detecting infants with primary CH, as well as cases of hypopituitary hypothyroidism, by follow-up of infants with a T4 below an absolute cutoff or with a... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3330321 Tue, 02 Mar 2010 10:06:17 +0100 3330321 A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation http://www.medworm.com/index.php?rid=3330320&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn5m65520229m7717%2F Abstract  Over the years, the mitochondrial fatty acid β-oxidation (FAO) pathway has been characterised at the biochemical level as well as the molecular biological level. FAO plays a pivotal role in energy homoeostasis, but it competes with glucose as the primary oxidative substrate. The mechanisms behind this so-called glucose–fatty acid cycle operate at the hormonal, transcriptional and biochemical levels. Inherited defects for most of the FAO enzymes have been identified and characterised and are currently included in neonatal screening programmes. Symptoms range from hypoketotic hypoglycaemia to skeletal and cardiac myopathies. The pathophysiology of these diseases is still not completely understood, hampering optimal treatment. Studies of patients and mouse models ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3330320 Tue, 02 Mar 2010 10:06:17 +0100 3330320 Combined hyperlipidemia in patients with lysinuric protein intolerance http://www.medworm.com/index.php?rid=3305500&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe25277lx54778562%2F Conclusion  Serum cholesterol and triglyceride values are markedly elevated in LPI patients. Although the mechanism of combined hyperlipidemia remains unknown and is not explained by fat consumption, hyperlipidemia is clearly progressive with age, suggesting that starting statin therapy early is probably beneficial. Statins are well-tolerated and efficacious in LPI. Content Type Journal ArticleCategory Research ReportDOI 10.1007/s10545-010-9050-5Authors Laura M. Tanner, University of Turku Department of Pediatrics Turku FinlandHarri Niinikoski, University of Turku Department of Pediatrics Turku FinlandKirsti Näntö-Salonen, University of Turku Department of Pediatrics Turku FinlandOlli Simell, University of Turku Department of Pediatrics Turku Finland Journal... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3305500 Tue, 23 Feb 2010 08:10:54 +0100 3305500 Four years of expanded newborn screening in Portugal with tandem mass spectrometry http://www.medworm.com/index.php?rid=3305501&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F68732705661765k6%2F Conclusions  Our data support the advantage of a centralised laboratory for screening an elevated number of samples and making decisions if relying on a clinical network able to provide fast treatment and a good outcome in the screened cases. Content Type Journal ArticleCategory Research ReportDOI 10.1007/s10545-010-9048-zAuthors Laura Vilarinho, Medical Genetics Center, National Institute of Health (INSA) Newborn Screening Unit Praca Pedro Nunes 88 4099-028 Porto PortugalHugo Rocha, Medical Genetics Center, National Institute of Health (INSA) Newborn Screening Unit Praca Pedro Nunes 88 4099-028 Porto PortugalCarmen Sousa, Medical Genetics Center, National Institute of Health (INSA) Newborn Screening Unit Praca Pedro Nunes 88 4099-028 Porto PortugalAna Marcão, Medica... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3305501 Tue, 23 Feb 2010 08:10:51 +0100 3305501 Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations http://www.medworm.com/index.php?rid=3305503&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw706540567870314%2F We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3305503 Tue, 23 Feb 2010 08:10:50 +0100 3305503 The risk of Parkinson’s disease in type 1 Gaucher disease http://www.medworm.com/index.php?rid=3305502&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm83864w41l229001%2F In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-010-9055-0Authors Gilberto Bultron, Yale University School of Medicine Department of Pediatrics and Internal Medicine 333 Cedar Street P.O. Box 208064 New Haven CT 06520-8064 USAKatherine Kacena, Yale University School of Medicine Department of Pediatrics and Internal Medicine 333 Cedar Street P.O. Box 208064 New Haven CT 06520-8064 USADaniel Pearson, Yale University School of Medicine Department of Pediatrics and Internal Medicine 333 Cedar Street P.O. Box 208064 New Haven CT 06520-8064 USAMichael Boxer, Arizona Hematology Oncology Tucson AZ USARuhua Yang, Yale University Sc... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3305502 Tue, 23 Feb 2010 08:10:50 +0100 3305502 The effects of early and late bone marrow transplantation in siblings with alpha-mannosidosis. Is early haematopoietic cell transplantation the preferred treatment option? http://www.medworm.com/index.php?rid=3286619&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1rukhk0204q3826%2F This article documents both the neurological and physical outcomes of the first published set of siblings undergoing transplantation at differing ages for α-mannosidosis. The older brother, the index case, was diagnosed at the age of 3 years and underwent transplantation at 13 years for the treatment of increasing somatic problems and recurrent infections. The younger brother had undergone transplantation pre-symptomatically at 6 months of age. Their clinical, radiological and developmental outcomes are documented and compared with the previous published cases, with the case for early transplantation being weighted against other potential therapies. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s10545-009-9035-4Authors A. A. Broomfield, Royal Manch... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3286619 Wed, 17 Feb 2010 18:32:17 +0100 3286619 The biochemical basis of hereditary fructose intolerance http://www.medworm.com/index.php?rid=3282678&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr51472j523n43771%2F Abstract  Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecula... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282678 Tue, 16 Feb 2010 18:09:37 +0100 3282678 Serum MIP-1 α level: a biomarker for the follow-up of lentiviral therapy in mucopolysaccharidosis IIIB mice http://www.medworm.com/index.php?rid=3282679&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F95m4373543857508%2F In this study, we examined the effect of brain-directed lentiviral (LV) gene therapy on serum levels of macrophage inflammatory protein 1 alpha (MIP-1α) and brain-derived neurotrophic factor (BDNF) proteins in the murine model of MPS IIIB to identify novel serum biomarkers. The cytokine MIP-1α was elevated in MPS IIIB mouse serum, and following gene therapy, it was reduced to normal levels. For neurotrophin BDNF, the difference in serum levels between MPS IIIB and normal mice was not statistically significant; after LV gene therapy, an increase in protein was found in treated mice, although the values were not statistically significant. Our studies suggest MIP-1α as the first serum biomarker that could be used to monitor disease progression and treatment for MPS IIIB disease. ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282679 Tue, 16 Feb 2010 18:09:35 +0100 3282679 Therapeutic approaches for neuronopathic lysosomal storage disorders http://www.medworm.com/index.php?rid=3282680&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F102w5415g76j7p4q%2F Abstract  Therapy of the central nervous system (CNS) manifestations of lysosomal storage diseases (LSDs) has remained a major challenge because of its inability to deliver therapeutic agents efficiently across the intact blood–brain barrier. Non-specific therapies such as hematopoietic stem cell transplantation have been useful in globoid cell leukodystrophy (Krabbe disease) and in some mucopolysaccharidoses. Anti-inflammatory agents also show promise as adjuvant therapy. High doses of replacement therapy with native or modified enzyme show renewed promise for correction of CNS cells. Alternatively, small molecules can enter the brain relatively easily and promote reduction of accumulated substrate or function as pharmacological chaperones to enhance the level of the def... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282680 Tue, 16 Feb 2010 18:09:34 +0100 3282680 Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur http://www.medworm.com/index.php?rid=3282682&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg06230460n772212%2F Abstract  Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by al... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282682 Tue, 16 Feb 2010 18:09:33 +0100 3282682 Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I http://www.medworm.com/index.php?rid=3282681&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg166406t20813846%2F In conclusion, blood and urine levels of DS and HS provide an intrinsic monitoring and screening tool for MPS I patients. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9036-3Authors Shunji Tomatsu, Saint Louis University Department of Pediatrics St. Louis MO USAAdriana M. Montaño, Saint Louis University Department of Pediatrics St. Louis MO USAToshihiro Oguma, Daiichi-Sankyo Co., Ltd Tokyo JapanVu Chi Dung, Saint Louis University Department of Pediatrics St. Louis MO USAHirotaka Oikawa, Saint Louis University Department of Pediatrics St. Louis MO USATalita Giacomet de Carvalho, Saint Louis University Department of Pediatrics St. Louis MO USAMaría L. Gutiérrez, Saint Louis University Department of Pediatrics St. Louis MO USASeiji Yamaguchi, Shimane U... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282681 Tue, 16 Feb 2010 18:09:33 +0100 3282681 The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach http://www.medworm.com/index.php?rid=3282683&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqxv8612p7005q128%2F Abstract  A pilot expanded newborn screening programme to detect inherited metabolic disorders by means of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) began in the Campania region, southern Italy, in 2007. By October 2009, >8,800 dried blood samples on filter paper from 11 hospitals had been screened. Within this screening programme, we identified a case of mitochondrial acetoacetyl-coenzyme A (CoA) thiolase deficiency [β-ketothiolase (β-KT) deficiency] by analysing the acylcarnitine profile from a dried blood spot with LC-MS/MS. Gas chromatography coupled with mass spectrometry analysis of urinary organic acids and LC-MS/MS analysis of urinary acylcarnitines were in line with this disorder. In fact, concentrations were well beyond the cut-of... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282683 Tue, 16 Feb 2010 06:42:05 +0100 3282683 Chorionic villi ultrastructure in the prenatal diagnosis of glycogenosis type II http://www.medworm.com/index.php?rid=3282684&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F078687253388156v%2F Conclusions  Ultrastructural findings correlated with biochemical and genetic results, providing a clear and early indicator of the definite diagnosis for future pregnancy management or an early therapeutic approach. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s10545-009-9033-6Authors Beatriz San Millan, University Hospital of Vigo, Meixoeiro Department of Pathology and Neuropathology Vigo 36200 SpainSusana Teijeira, University Hospital of Vigo, Meixoeiro Department of Pathology and Neuropathology Vigo 36200 SpainCarmen Domínguez, Hospital Universitari Vall d’Hebron, Centre for Biomedical Research on Rare Diseases (CIBERER) Biochemistry and Molecular Biology Research Center Barcelona SpainIrene Vieitez, University Hospital of Vigo, Meixoeiro Departm... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3282684 Tue, 16 Feb 2010 06:42:03 +0100 3282684 Biochemical abnormalities in a patient with thymidine phosphorylase deficiency with fatal outcome http://www.medworm.com/index.php?rid=3270846&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fml08h27466360715%2F This report shows that TP deficiency is a severe clinical condition with a broad spectrum of affected tissues. TP deficiency can be easily determined by the measurement of pyrimidine metabolites in body fluids and TP activity in peripheral blood leucocytes. Early detection and treatment may prevent the progress of the clinical symptoms and, therefore, should be considered for inclusion in newborn screening programmes. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s10545-010-9049-yAuthors Jaap A. Bakker, Maastricht University Medical Centre Department of Clinical Genetics, Laboratory for Biochemical Genetics P. Debyelaan 25 6229 HX Maastricht The NetherlandsPatrick Schlesser, CHC Clinique de l’Espérance Department of Paediatrics Montegnée-Liege BelgiumHubert J. M. ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270846 Fri, 12 Feb 2010 07:14:42 +0100 3270846 Long-term correction of murine phenylketonuria by viral gene transfer: liver versus muscle http://www.medworm.com/index.php?rid=3270847&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F54645v321522n562%2F Abstract  Current therapy for phenylketonuria (PKU) consists of life-long dietary restriction of phenylalanine (Phe), which presents problems of adherence for patients. Alternative therapies under investigation include, among others, the use of gene therapy to provide copies of wild-type, non-mutant, phenylalanine hydroxylase (PAH) enzyme. Expression of PAH in both liver (the usual metabolic source of this enzyme) and skeletal muscle is under investigation. Liver gene therapy, using a viral vector based on the adeno-associated viruses (AAVs), provided effective clearance of serum Phe that was sustained for 1 year in some mice. In order for PAH expression to be effective in skeletal muscle, the essential metabolic cofactor, tetrahydrobiopterin (BH4), must also be provide... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270847 Fri, 12 Feb 2010 07:14:40 +0100 3270847 Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites http://www.medworm.com/index.php?rid=3270848&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl02p17ru5v820160%2F Abstract  Phenylketonuria (PKU) is a metabolic genetic disease characterized by deficient phenylalanine hydroxylase (PAH) enzymatic activity. Brain hypomyelination has been reported in untreated patients, but its mechanism remains unclear. We therefore investigated the influence of phenylalanine (Phe), phenylpyruvate (PP), and phenylacetate (PA) on oligodendrocytes. We fisrt showed in a mouse model of PKU that the number of oligodendrocytes is not different in corpus callosum sections from adult mutants or from control brains. Then, using enriched oligodendroglial cultures, we detected no cytotoxic effect of high concentrations of Phe, PP, or PA. Finally, we analyzed the impact of Phe, PP, and PA on the myelination process in myelinating cocultures using both an in vitro in... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270848 Fri, 12 Feb 2010 07:14:38 +0100 3270848 Disease mechanisms and protein structures in fatty acid oxidation defects http://www.medworm.com/index.php?rid=3270850&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2v216132187g1uh8%2F Abstract  In fatty acid oxidation defects, the majority of gene variations are of the missense type and, therefore, prone to inducing misfolding in the resulting mutant protein. The fate of the mutant protein depends on the nature of the gene variation and other genetic factors as well as cellular and environmental factors. Since it has been shown that certain fatty acid oxidation enzyme proteins, exemplified by mutant medium-chain and short-chain acyl-CoA dehydrogenases as well as electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase, may accumulate during cellular stress, e.g. elevated temperature, there is speculation about how such proteins may disturb the integrity of the putative fatty acid oxidation metabolone, in which the two flavoproteins... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270850 Fri, 12 Feb 2010 07:14:35 +0100 3270850 Fructose 1,6-bisphosphatase deficiency: enzyme and mutation analysis performed on calcitriol-stimulated monocytes with a note on long-term prognosis http://www.medworm.com/index.php?rid=3270849&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2777286134785865%2F In conclusion, we present a reliable diagnostic system to verify an FBPase deficiency and find the genetic aberration. Content Type Journal ArticleCategory Research ReportDOI 10.1007/s10545-009-9034-5Authors Cristine Åsberg, Sahlgrenska University Hospital Department of Clinical Chemistry and Transfusion Medicine 41345 Gothenburg SwedenOla Hjalmarson, University of Gothenburg Department of Paediatrics, Children’s Hospital Gothenburg SwedenJan Alm, Karolinska University Hospital Astrid Lindgrens Children’s Hospital Stockholm SwedenTommy Martinsson, University of Gothenburg Department of Clinical Genetics Gothenburg SwedenJohan Waldenström, Sahlgrenska University Hospital Department of Clinical Chemistry and Transfusion Medicine 41345 Gothenburg SwedenChristina Hellerud, Sahlgren... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270849 Fri, 12 Feb 2010 07:14:35 +0100 3270849 Nutritional issues in treating phenylketonuria http://www.medworm.com/index.php?rid=3270851&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh510716801855w16%2F Abstract  A phenylalanine (Phe)-restricted diet is the mainstay of phenylketonuria (PKU) treatment, and, in recent years, the nutritional management of PKU has become more complex in order to optimize patients’ growth, development and diet compliance. Dietary restriction of Phe creates a diet similar to a vegan diet, and many of the nutritional concerns and questions applicable to vegans who wish to avoid animal products are also relevant to patients with PKU. Owing to their nutritional characteristics, breast milk and breastfeeding should be given greater consideration as a useful food in patients with PKU and in those with other inborn errors of metabolism. Further key issues for consideration include the quality of the available amino acid substitutes, the neurotrophic... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270851 Fri, 12 Feb 2010 07:14:34 +0100 3270851 Diet and visually significant cataracts in galactosaemia: is regular follow up necessary? http://www.medworm.com/index.php?rid=3270852&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1240u281761x6775%2F Conclusion  Cataracts affecting vision were not found in our cohort. A direct relationship between dietary compliance and cataract formation was not demonstrated. On the basis of our data, regular life-long ophthalmic exam of patients with classic galactosemia seems to be unnecessary. Take-home message  Cataracts which develop in patients with classical Galactosaemia do not usually affect vision and may be unrelated to compliance to diet. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9042-5Authors John Widger, Children’s University Hospital The National Centre for Inherited Metabolic Disorders Dublin IrelandJennifer O’Toole, Children’s University Hospital The National Centre for Inherited Metabolic Disorders Dublin ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270852 Fri, 12 Feb 2010 07:14:33 +0100 3270852 Classical galactosemia in Estonia: selective neonatal screening, incidence, and genotype/phenotype data of diagnosed patients http://www.medworm.com/index.php?rid=3270853&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp5882k64w8q67374%2F Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s10545-010-9045-2Authors Katrin Õunap, Tartu University Hospital Department of Genetics, United Laboratories 2 Puusepa Street Tartu 51014 EstoniaKairit Joost, University of Tartu The Centre of Excellence for Translational Medicine Tartu EstoniaTriinu Temberg, Asper Biotech Tartu EstoniaKülliki Krabbi, Central Laboratory of Health Protection Inspectorate Tallinn EstoniaNeeme Tõnisson, Tartu University Hospital Department of Genetics, United Laboratories 2 Puusepa Street Tartu 51014 Estonia Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270853 Fri, 12 Feb 2010 07:14:30 +0100 3270853 Erratum to: Long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam] as a possible model to study renal disease in methylmalonic acidurias http://www.medworm.com/index.php?rid=3270854&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmj1q852g46321178%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10545-010-9064-zAuthors S. W. Sauer, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 153 69120 Heidelberg GermanyS. Opp, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 153 69120 Heidelberg GermanyA. Haarmann, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 153 69120 Heidelberg GermanyJ. G. Okun, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 153 69120 Heidelberg GermanyS. Kölker, U... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3270854 Thu, 11 Feb 2010 11:39:25 +0100 3270854 Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase http://www.medworm.com/index.php?rid=3248398&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5840068768m62676%2F Abstract  Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96&n... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3248398 Fri, 05 Feb 2010 18:18:08 +0100 3248398 An overview of a cohort of South African patients with mitochondrial disorders http://www.medworm.com/index.php?rid=3248399&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3u846q2552272278%2F The objective of this paper is to describe the profile of patients with mitochondrial disorders in South Africa. Patients with possible mitochondrial disorders were accessed over 10 years. Analyses for respiratory chain and pyruvate dehydrogenase complex enzymes were performed on muscle. A diagnosis of a mitochondrial disorder was accepted only if an enzyme activity was deficient. Sixty-three patients were diagnosed with a mitochondrial disorder, including 40 African, 20 Caucasian, one mixed ancestry, and two Indian patients. The most important findings were the difference between African patients and other ethnicities: respiratory chain enzyme complexes CI+III or CII+III deficiencies were found in 52.5% of African patients, being of statistical significance (p value = 0.0061). T... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3248399 Fri, 05 Feb 2010 07:57:38 +0100 3248399 A novel mutation in LMBRD1 causes the cblF defect of vitamin B12 metabolism in a Turkish patient http://www.medworm.com/index.php?rid=3242669&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2433j665348k3077%2F Abstract  In the cblF defect of vitamin B12 (cobalamin) metabolism, cobalamin is trapped in lysosomes. Consequently, cobalamin coenzyme synthesis is blocked, and cofactors for methionine synthase and methylmalonyl-coenzyme A (CoA) mutase are deficient. We recently identified LMBRD1 as the causative gene located on chromosome 6q13 and showed that 18 out of 24 alleles in unrelated patients carried the deletion c.1056delG (p.L352fsX18) (Rutsch et al. (Nat Genet 41:234–239, 2009). LMBRD1 encodes the lysosomal membrane protein LMBD1, which presumably facilitates lysosomal cobalamin export. Our patient is the second child of consanguineous Turkish parents. He presented on the second day of life with cerebral seizures due to intraventricular hemorrhage. Plasma homocysteine and uri... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3242669 Tue, 02 Feb 2010 17:52:29 +0100 3242669 A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency http://www.medworm.com/index.php?rid=3234599&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg4m5333881061j17%2F Conclusion  EGP was severely hampered in both patients, resulting in hypoglycemia. However, despite defective hepatic and renal GNG in both disorders and defective hepatic GGL in GSD-1a, both patients were still able to produce glucose via both pathways. As all necessary enzymes of these pathways have now been functionally detected in muscle, a contribution of muscle to EGP during fasting via both GGL as well as GNG is suggested. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9030-9Authors Hidde H. Huidekoper, University Hospital of Amsterdam Department of Pediatrics (G8-205) Academic Medical Center PO Box 22660 NL-1100 DD Amsterdam The NetherlandsGepke Visser, University Medical Center Utrecht Wilhelmina Children’s Hospital Utrecht The... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3234599 Mon, 01 Feb 2010 18:07:41 +0100 3234599 PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease http://www.medworm.com/index.php?rid=3224643&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa75n868374632604%2F Abstract  Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but f... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3224643 Wed, 27 Jan 2010 19:55:44 +0100 3224643 Mouse models for nuclear DNA-encoded mitochondrial complex I deficiency http://www.medworm.com/index.php?rid=3224645&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqv11520243p5r837%2F Abstract  Mitochondrial diseases are a group of heterogeneous pathologies with decreased cellular energy production as a common denominator. Defects in the oxidative phosphorylation (OXPHOS) system, the most frequent one in humans being isolated complex I deficiency (OMIM 252010), underlie this disturbed-energy generation. As biogenesis of OXPHOS complexes is under dual genetic control, with complex II being the sole exception, mutations in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) are found. Increasing knowledge is becoming available with respect to the pathophysiology and cellular consequences of OXPHOS dysfunction. This aids the rational design of new treatment strategies. Recently, the first successful treatment trials were carried out in patient-d... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3224645 Wed, 27 Jan 2010 19:55:41 +0100 3224645 Genotype–phenotype correlations: sudden death in an infant with very-long-chain acyl-CoA dehydrogenase deficiency http://www.medworm.com/index.php?rid=3224644&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9035743757473891%2F We present a patient who died as a result of fatal hypoglycemia at 38 h of life before diagnosis of VLCADD could be established by newborn screening. Despite the early onset of the disease, the patient was found to have a missense mutation within the ACADVL gene with a c.848T>C, c.342+1G>C genotype. Genotype alone remains limited in its predictive ability to determine which affected individuals are at risk for fatal complications. Content Type Journal ArticleCategory Case ReportDOI 10.1007/s10545-009-9041-6Authors Curtis R. Coughlin, Section of Biochemical Genetics, The Children’s Hospital of Philadelphia 34th& Civic blvd. 9S23 Philadelphia PA 19104 USACan Ficicioglu, Section of Biochemical Genetics, The Children’s Hospital of Philadelphia 34th& Civic blvd. 9S23 Philadelp... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3224644 Wed, 27 Jan 2010 19:55:41 +0100 3224644 Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography–tandem mass spectrometry http://www.medworm.com/index.php?rid=3224646&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg173w6066297671w%2F Abstract  Mucopolysaccharidosis type IVA (MPS IVA, Morquio A disease), a progressive lysosomal storage disease, causes skeletal chondrodysplasia through excessive storage of keratan sulfate (KS). KS is synthesized mainly in cartilage and released to the circulation. The excess storage of KS disrupts cartilage, consequently releasing more KS into circulation, which is a critical biomarker for MPS IVA. Thus, assessment of KS level provides a potential screening strategy and determines clinical course and efficacy of therapies. We have recently developed a tandem mass spectrometry liquid chromatography [LC/MS/MS] method to assay KS levels in blood. Forty-nine blood specimens from patients with MPS IVA [severe (n = 33), attenuated (n = 11) and undefined (n =... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3224646 Wed, 27 Jan 2010 19:55:40 +0100 3224646 Social-adaptive and psychological functioning of patients affected by Fabry disease http://www.medworm.com/index.php?rid=3196633&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj537507152736071%2F This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years. Content Type Journal ArticleCategory Research ReportDOI 10.1007/s10545-009-9025-6Authors Dawn Alyssia Laney, Em... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3196633 Tue, 19 Jan 2010 17:46:21 +0100 3196633 Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry http://www.medworm.com/index.php?rid=3192529&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7521678128810723%2F Conclusions  Neurological manifestations of GD often begin to appear before the age of 2 years. The most common neurological signs and manifestations are brainstem abnormalities and fine motor dysfunction. The most common genotype is L444P/L444P. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9009-6Authors Anna Tylki-Szymańska, The Children’s Memorial Health Institute Clinic of Metabolic Diseases, Endocrinology and Diabetology Al. Dzieci Polskich 20 04 736 Warsaw PolandAshok Vellodi, Great Ormond Street Children’s Hospital NHS Trust London UKAmal El-Beshlawy, Pediatric Hospital of Cairo University Cairo EgyptJ. Alexander Cole, Biostatistics/Epidemiology, Biomedical Data Sciences and Informatics, Genzyme Corporation Cambridge MA USA... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3192529 Mon, 18 Jan 2010 18:49:31 +0100 3192529 Storage correction in cells of patients suffering from mucopolysaccharidoses types IIIA and VII after treatment with genistein and other isoflavones http://www.medworm.com/index.php?rid=3192530&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn93637247l11j2nl%2F Abstract  Mucopolysaccharidoses are autosomal and recessive lysosomal storage disorders caused by the deficiency of a lysosomal enzyme involved in glycosaminoglycan catabolism. The Sanfilippo type A disease (MPS III A) results from sulfamidase deficiency, which leads to accumulation of heparan sulfate, whereas Sly disease (MPS VII) results from beta-glucuronidase deficiency, leading to accumulation of heparan, dermatan, and chondroitin sulfates. These syndromes are characterized by severe central nervous system degeneration, resulting in progressive mental retardation, and fatality occurs in severely affected children. To date, no effective treatment is available except for bone marrow transplantation in specific cases. Recently, the use of genistein, an isoflavone that inh... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3192530 Mon, 18 Jan 2010 18:49:29 +0100 3192530 Aberrant synthesis of ATP synthase resulting from a novel deletion in mitochondrial DNA in an African patient with progressive external ophthalmoplegia http://www.medworm.com/index.php?rid=3192531&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp601177mm2t28661%2F Abstract  A young, adult, African male patient presented with progressive proximal muscle weakness, external ophthalmoplegia and ptosis, as well as cardiac conduction abnormalities resembling Kearns–Sayre syndrome (KSS). Magnetic resonance imaging (MRI) of the brain revealed normal basal ganglia but bilateral well-circumscribed lesions in the cerebellar peduncles. Enzyme deficiencies in oxidative phosphorylation (OXPHOS) complexes I, IV and V was measured in muscle tissue. Blue native polyacrylamide gel electrophoresis (BN-PAGE) confirmed decreased protein content and activity of these complexes and revealed the presence of two catalytically active complex V sub-complexes. Upon investigation by molecular genetics, the mitochondrial DNA (mtDNA) copy number was found to be ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3192531 Fri, 15 Jan 2010 18:02:35 +0100 3192531 Xanthine dehydrogenase deficiency with novel sequence variations presenting as rheumatoid arthritis in a 78-year-old patient http://www.medworm.com/index.php?rid=3192532&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F14326u188386555r%2F Conclusion  Hereditary xanthinuria is a rare disorder, but it also needs to be considered in patients not originating from Mediterranean countries or the Near or Middle East. Urate concentration in serum and urine may provide an initial indication of XDH deficiency before high-performance liquid chromatography (HPLC) analysis is performed. The key to identifying the disorder is a greater awareness of XDH deficiency amongst primary care physicians, nephrologists, and urologists, but also rheumatologists. The diagnosis and therapeutic management requires a multidisciplinary approach. Content Type Journal ArticleCategory Research ReportDOI 10.1007/s10545-009-9011-zAuthors Agnieszka Jurecka, The Children’s Memorial Health Institute Department of Metabolic Diseases, End... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3192532 Fri, 15 Jan 2010 00:45:49 +0100 3192532 Post-ictal psychosis in adolescent Niemann-Pick disease type C http://www.medworm.com/index.php?rid=3178057&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F50p1gx106x668040%2F We describe the presentation of an adolescent with juvenile-onset Niemann-Pick disease type C (NPC) who presented with post-ictal psychosis in the context of a developing seizure disorder. After demonstrating mild gait disturbance beginning at the age of 4 years, he was diagnosed with NPC at age 12 on the basis of 95% of cultured fibroblasts staining positive for filipin and a reduced fibroblast cholesterol esterification rate. He then developed a seizure disorder at age 15, where clusters of seizures produced typical psychotic symptoms, including hallucinations and delusions. His seizure disorder responded to valproate, which resulted in a settling of his psychotic symptoms. Whilst post-ictal psychosis is rarely reported prior to the age of 16, NPC in adolescents and adults is parti... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3178057 Wed, 13 Jan 2010 06:45:48 +0100 3178057 Clinical and biochemical monitoring of patients with fatty acid oxidation disorders http://www.medworm.com/index.php?rid=3170397&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft56746v35426r539%2F Abstract  Evidence-based guidelines for monitoring patients with disorders in fatty acid oxidation (FAO) are lacking, and most protocols are based on expert statements. Here, we describe our protocol for Danish patients. Clinical monitoring is the most important measure and has the main aims of checking growth, development and diet and of bringing families to the clinic regularly to remind them of their child’s risk and review how they cope and adjust, e.g. to an acute intercurrent illness. Most of these measures are simple and can be carried out during a routine out-patient visit; we seldom do more complicated assessments by a neuropsychologist, speech therapist, or physical and occupational therapists. Paraclinical measurements are not used for short-chain and medium-ch... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3170397 Mon, 11 Jan 2010 18:22:53 +0100 3170397 Tetrahydrobiopterin responsiveness after extended loading test of 12 Danish PKU patients with the Y414C mutation http://www.medworm.com/index.php?rid=3162803&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhwr903j7u962vh40%2F Abstract  Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phe accumulation can lead to cognitive impairment. Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations. We tested 12 patients with PKU, 8–29 years of age, all carrying the common Y414C mutation in the PAH gene. Three were homozygous and nine were compound heterozygous, with the second mutation being a putative null mutation. During the study period, genuine protein was increased to approximately 1 g/kg. The patients were treated with 20, 10, and 5 mg BH4/kg/day for 1 week on each dose, start... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3162803 Fri, 08 Jan 2010 21:40:50 +0100 3162803 Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder http://www.medworm.com/index.php?rid=3162804&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe6hv606595526740%2F Abstract  Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of structurally abnormal, amylopectin-like glycogen in affected tissues. The accumulated glycogen lacks multiple branch points and thus has longer outer branches and poor solubility, causing irreversible tissue and organ damage. Although classic GSD IV presents with early onset of hepatosplenomegaly with progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity with respect to age at onset and variability in pattern and extent of organ and tissue involvement. With the advent of cloning and determination of the genomic structure of the human GBE gene (GBE1), molecular analysis and characterizati... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3162804 Thu, 07 Jan 2010 22:23:27 +0100 3162804 A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy http://www.medworm.com/index.php?rid=3155435&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47330775385n7g82%2F Conclusions  Our results suggest that excessive prenatal GABA exposure in the central nervous system (CNS) was responsible for the clinical manifestations of GABA transaminase deficiency. Our findings suggest the dual nature of GABA as an excitatory molecule early in life, followed by a functional switch to an inhibitory species later in development. Furthermore, quantitative 1H-MRS appears to be a useful, noninvasive tool for detecting inborn errors of GABA metabolism in the CNS. Content Type Journal ArticleCategory Rapid CommunicationDOI 10.1007/s10545-009-9022-9Authors Megumi Tsuji, Kanagawa Children’s Medical Center Division of Neurology, Clinical Research Institute 2-138-4 Mutsukawa, Minami-ku Yokohama 232-8555 JapanNoriko Aida, Kanagawa Children’s Medical Cen... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155435 Tue, 05 Jan 2010 17:02:01 +0100 3155435 The monitoring of trace elements in blood samples from patients with inborn errors of metabolism http://www.medworm.com/index.php?rid=3155436&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb01k52m8v377u520%2F Abstract  Patients having inborn errors of intermediary metabolism (IEMs) may have element deficiencies related to dietary treatment. Our objective was to study several elements [cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), manganese (Mn), molybdenum (Mo) and magnesium (Mg)] in patients with IEMs with and without dietary treatment and to compare these results with those established in a healthy paediatric population. We studied 72 patients with IEMs (age range 2 months–44 years; median 10.5 years), with and without protein-restricted dietary treatment. Control values were established in 92 subjects (age range 1 day–42 years; median 6.5 years). Dietary treatment consisted of a natural protein-restricted diet supplemented with a special... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155436 Tue, 05 Jan 2010 17:01:59 +0100 3155436 Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution http://www.medworm.com/index.php?rid=3155437&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftn3600w368437854%2F We present an 11-year-old girl affected by the severe form of MPS-II who was followed up over a time span of 8 years, focusing on clinical and brain MRI evolution. In the last 2.5 years, the patient has been treated with enzyme replacement therapy (ERT) with idursulfase (Elaprase™, Shire Human Genetic Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in our patient did not differ from those detected in male patients: J-shaped pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2-hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT introduction, whereas perivascular space enlargement did not change significantly before and ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155437 Tue, 05 Jan 2010 17:01:58 +0100 3155437 Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5′-phosphate availability http://www.medworm.com/index.php?rid=3155438&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw4054u6227r05573%2F We describe two neonates presenting with perinatal hypophosphatasia and severe epileptic encephalopathy resulting in death. Both had increased levels of urinary vanillactate, indicating functional deficiency of aromatic amino acid decarboxylase, a pyridoxal-5-phosphate (PLP)-dependent enzyme required for dopamine and serotonin biosynthesis. Clinical findings and results of subsequent metabolic investigations were consistent with secondary pyridoxine-deficient encephalopathy. These patients highlight the importance of tissue non-specific alkaline phosphatase in the neuronal PLP-dependent metabolism of neurotransmitters. In addition, the disturbance of PLP metabolism appears to underlie the predominant neurological presentation in our patients. We recommend the measurement of serum alk... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155438 Mon, 04 Jan 2010 17:59:40 +0100 3155438 Abnormal nonstoring capillary endothelium: a novel feature of Gaucher disease. Ultrastructural study of dermal capillaries http://www.medworm.com/index.php?rid=3155439&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw01834p3u5575913%2F Abstract  Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD) patients (types II and III) revealed hitherto unknown alteration of the blood capillary endothelial cells (ECs) featured by hypertrophy and numerous subplasmalemmal microvesicles underneath both the apical and basal membranes. There was also prominent apical membrane folding with formation of filiform and large cytoplasmic projections, with occasional transcapillary cytoplasmic bridges. Similar, though less frequently expressed, changes were manifested at the basal membrane by numerous cytoplasmic projections into the subendothelial space. Regressive changes with EC breakdown were rare. Lysosomal storage was always absent. Besides EC hypertrophy, there was also increased EC density in the ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155439 Mon, 04 Jan 2010 17:59:39 +0100 3155439 Fatty acid oxidation disorders: outcome and long-term prognosis http://www.medworm.com/index.php?rid=3155441&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5243p747k9466u46%2F Abstract  Assessing the outcome of fatty acid oxidation disorders is difficult, as most are rare. For diagnosis by newborn screening, the situation is compounded: far more cases are diagnosed by screening than by clinical presentation, representing a somewhat different cohort. The literature on outcome was reviewed. For disorders other than medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency there was insufficient evidence to make many firm statements. In MCAD deficiency, risk of death in the first 72 h is around 4%, with a further approximately 5–7% fatality rate in the first 6 years but very low subsequent risk in previously undiagnosed patients. The risk of death after diagnosis is very low at any age, with good management. The long-term ou... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155441 Mon, 04 Jan 2010 17:59:37 +0100 3155441 Tumoral calcinosis http://www.medworm.com/index.php?rid=3155440&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv13qnpj760653181%2F Content Type Journal ArticleCategory Images in Metabolic MedicineDOI 10.1007/s10545-009-9019-4Authors Mirian C. H. Janssen, Radboud University Medical Centre Department of General Internal Medicine PO Box 9101 6500 HB Nijmegen The NetherlandsRuud G. L. de Sévaux, Radboud University Medical Centre Department of Nephrology Nijmegen The Netherlands Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155440 Mon, 04 Jan 2010 17:59:37 +0100 3155440 Study of inborn errors of metabolism in urine from patients with unexplained mental retardation http://www.medworm.com/index.php?rid=3155442&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7827121727150h7%2F In conclusion, in patients with MR, it is essential to perform a thorough appraisal of the associated signs and symptoms, and in most disorders, it is necessary to apply specific analyses. In some cases, it is important to achieve an early diagnosis and therapy, which may reduce the morbimortality, and to offer genetic counselling. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9004-yAuthors Angela Sempere, Pediatric Neurology, Hospital Sant Joan de Déu, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII Esplugues SpainAngela Arias, Hospital Clínic and CIBERER, ISCIII Division of Inborn Errors of Metabolism (IBC), Department of Biochemistry and Molecular Genetics Barcelona SpainGuillermo Farré, Hospital Clínic and CIBE... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155442 Mon, 04 Jan 2010 17:59:35 +0100 3155442 Pediatric Gaucher disease type I and mild growth hormone deficiency: a new feature? http://www.medworm.com/index.php?rid=3155444&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb376432388q64712%2F Abstract  A 5-year-old girl was referred to the Department of Pediatrics and Neonatology, Guglielmo da Saliceto Hospital, Italy, because of growth retardation. Clinical and laboratory investigations showed pallor, hepatosplenomegaly, anemia and low/normal platelet count. Further investigations led to the diagnosis of Gaucher disease (GD). We believe this is the first report of growth hormone deficiency in a growth-retarded child with GD. After 1 year of imiglucerase replacement enzyme therapy, her bone age had normalized, linear growth rate had accelerated, and insulin growth factor-1 (IGF-1) and, perhaps more interestingly, growth hormone deficiency, had normalized. While the pathophysiological mechanisms underlying compromised growth in GD are poorly understood, the ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155444 Mon, 04 Jan 2010 17:59:33 +0100 3155444 Disease severity in sibling pairs with type 1 Gaucher disease http://www.medworm.com/index.php?rid=3155443&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb0482x1593j625v2%2F Abstract  The only prognostic markers in Gaucher disease, the most common lysosomal storage disorder, are young age at first symptom/sign and the presence of null/severe mutations, both being predictive of more severe phenotypes. Therefore, it would be helpful to know whether siblings with the same genotype can be expected to experience comparable phenotypic expression. All non-neuronopathic sibling pairs in our referral clinic (1993–2008) with the same genotype were included. For each pair, gender, date of birth, severity score index at presentation, age at diagnosis and first symptom/sign, presence of bone involvement, spleen status, and use of enzyme replacement therapy were tabulated. There were 90 pairs of siblings: two sets of identical twins; 24 pairs of brothers, ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3155443 Mon, 04 Jan 2010 17:59:33 +0100 3155443 Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes—possibility for newborn screening http://www.medworm.com/index.php?rid=3121844&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx35622099022l137%2F Conclusion  The fluorometric technique for the assessment of GAA activity in DBS provides a reliable diagnosis for all variants of Pompe disease. The assay protocol could be simplified for neonatal screening, without increasing the false positive rate significantly or burdening the laboratory with time-consuming procedures. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-9003-zAuthors Zoltan Lukacs, University Medical Center of Hamburg-Eppendorf Institute of Clinical Chemistry Hamburg GermanyPaulina Nieves Cobos, University Medical Center of Hamburg-Eppendorf Institute of Clinical Chemistry Hamburg GermanyEugen Mengel, University of Mainz Department of Pediatrics Mainz GermanyRalf Hartung, University of Mainz Department of Pediatrics Mainz G... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3121844 Wed, 23 Dec 2009 22:57:21 +0100 3121844 Zellweger syndrome with unusual findings: non-immune hydrops fetalis, dermal erythropoiesis and hypoplastic toe nails http://www.medworm.com/index.php?rid=3121846&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnl6rlv41633v873u%2F We report here on a Turkish patient who presented with unusual clinical findings, that included non-immune hydrops, dermal erythropoiesis and hypoplastic toenails, as well as common dysmorphic features of Zellweger syndrome. The patient has also pulmonary hypoplasia, which has been reported in only a few patients with Zellweger syndrome. A peroxisomal biogenesis disorder was confirmed by enzyme analysis and abnormal very long-chain fatty acid (VLCFA) profiles in plasma and fibroblast and immunofluorescence microscopy studies. Subsequent molecular genetic analysis revealed a homozygous c.856C>T mutation (R268X) in the PEX3 gene, which made this patient the third to have a defect in this gene. In contrast to those of the two previously reported patients, the cells of this patient st... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3121846 Wed, 23 Dec 2009 22:57:20 +0100 3121846 Tyrosinemia type 1 and Angelman syndrome due to paternal uniparental isodisomy 15 http://www.medworm.com/index.php?rid=3121845&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw1x85465w7822w2n%2F Abstract  Uniparental isodisomy arises when an individual inherits two copies of a specific chromosome from a single parent, which can unmask a recessive mutation or cause a problem of genetic imprinting. Here we describe an exceptional case in which the patient simultaneously presents tyrosinemia type 1 and Angelman syndrome. The genetic studies showed that the patient presents paternal uniparental isodisomy of chromosome 15, with absence of the maternal homolog. As a consequence of this isodisomy, the patient is homozygous for the mutation IVS12+5G>A in the FAH gene, located in the chromosomal region 15q23-25, causing tyrosinemia type 1. The mutation was inherited from his father in double dosage, whereas the mother is not a carrier, which implies that the recurrence ri... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3121845 Wed, 23 Dec 2009 22:57:20 +0100 3121845 False-positive newborn screening mimicking glutaric aciduria type I in infants with renal insufficiency http://www.medworm.com/index.php?rid=3121847&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw647u88777711300%2F Abstract  Glutaric aciduria type I (GA I), an autosomal-recessive deficiency of glutaryl-CoA-dehydrogenase, leads to encephalopathic crises resulting in irreversible neurological damage. As early diagnosis and implementation of appropriate treatment has significant benefit for these patients, GA I has been implemented in the extended newborn screening program in several countries. Screening parameter is glutarylcarnitine (C5DC) with its ratios. From 1 January 2005 until 31 December 2008, 173,846 newborns were examined by neonatal screening in our screening center. C5DC and/or at least three C5DC/acylcarnitine ratios were increased in 53 newborns (0.03%) and persisted in 11 infants after recall. GA I was not confirmed in any of these infants, but all 11 infants were sufferin... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3121847 Wed, 23 Dec 2009 22:57:19 +0100 3121847 Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population http://www.medworm.com/index.php?rid=3121848&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F58873tl47k563863%2F Abstract  Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Δ4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common allele... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3121848 Wed, 23 Dec 2009 22:57:18 +0100 3121848 Erratum to: Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters http://www.medworm.com/index.php?rid=3016821&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2p8g722560l1585%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10545-009-9957-xAuthors F. Hörster, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 430 69120 Heidelberg GermanyS. F. Garbade, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 430 69120 Heidelberg GermanyT. Zwickler, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 430 69120 Heidelberg GermanyH. I. Aydin, Hacettepe University Ankara Department of Metabolism, Children’s Hospital Ankara TurkeyO. A. Bodamer, Allgemeines Krankenhaus Department of Paediatrics Vienna AustriaA... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3016821 Thu, 19 Nov 2009 07:32:48 +0100 3016821 Psychological aspects of patients with Fabry disease http://www.medworm.com/index.php?rid=3016823&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh214712178471314%2F In this study, 28 patients with Fabry disease completed the MMPI-2 and a background questionnaire. Fabry disease patients scored significantly higher than the MMPI-2 normative sample on seven clinical scales (Hs, D, Hy, Pd, Pa, Pt, Sc) and two validity scales (L, F). Individuals with elevated scores on the Hs, D, and Hy scales tend to have somatic complaints, sadness, and emotional distress. Under stress, they may experience an increase in physical symptoms. Elevated Pd, Pa, Pt, and Sc scales suggest social maladjustment, suspiciousness, and feelings of isolation. An elevated L scale suggests defensiveness; a high score on F suggests emotional turmoil. When compared with cohorts of patients with Gaucher disease (GD), chronic heart disease (CRHD), and chronic pain, the Fabry disease pati... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3016823 Thu, 19 Nov 2009 07:32:36 +0100 3016823 PDH E1β deficiency with novel mutations in two patients with Leigh syndrome http://www.medworm.com/index.php?rid=3016822&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh41435l8410h5t43%2F We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E1 activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. S... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3016822 Thu, 19 Nov 2009 07:32:36 +0100 3016822 Substrate deprivation therapy in juvenile Sandhoff disease http://www.medworm.com/index.php?rid=2971744&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7lv069654702r33%2F Summary  Substrate deprivation therapy has been successfully applied in a number of lysosomal storage diseases, such as Gaucher disease. So far only limited experience is available in Sandhoff disease. We initiated substrate deprivation therapy in one male patient, who initially presented at the age of 3.5 years with epilepsy and regression in motor skills and speech development. Juvenile Sandhoff disease was diagnosed on the basis of a decreased hexosaminidase activity in leukocytes and a homozygous HEXB gene mutation. After the epilepsy was controlled, the clinical course remained stable for years, defined by a mild proximal myopathy and stable mental retardation. At 14 years of age the patient experienced a second episode with progressively worsening general condition wit... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2971744 Fri, 06 Nov 2009 19:34:22 +0100 2971744 Miglustat therapy in juvenile Sandhoff disease http://www.medworm.com/index.php?rid=2971745&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu2u8852j3g068556%2F Summary  GM2-gangliosidosis is a rare and heterogeneous inherited metabolic disorder caused by autosomal recessive mutations in genes encoding the lysosomal enzyme β-hexosaminidase, resulting in the accumulation of ganglioside GM2 in various tissues, particularly the central nervous system. It is characterized by progressive neurological deterioration that mainly affects motor and spinocerebellar function. Several forms of GM2-gangliosidosis exist, including the Sandhoff variant. Currently there is no treatment for these conditions, except for palliative care. Miglustat (Zavesca) is a reversible inhibitor of glucosylceramide synthase, which catalyses the first committed step in the synthesis of glucose-based glycolipids. Miglustat has pharmacokinetic properties that allow it... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2971745 Fri, 06 Nov 2009 19:34:21 +0100 2971745 Heterozygous familial hypercholesterolaemia in childhood: Cardiovascular risk prevention http://www.medworm.com/index.php?rid=2971746&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu777j213665135l5%2F Summary  Children with familial hypercholesterolaemia (FH) have severely increased low-density lipoprotein cholesterol (LDL-C) levels that strongly predispose to premature cardiovascular disease (CVD) later in life. Early identification makes it possible to start lipid-lowering therapy at young age to prevent CVD. The atherosclerotic process can be inhibited by potent lipid-lowering therapy. The cornerstone of lipid-lowering therapy is a healthy lifestyle, but most of the time this is insufficient to reach adequate LDL-C goals. Subsequently, pharmacological therapy is initiated with increasing frequency. In the past decade numerous studies have assessed the efficacy and safety of statins in children with FH. Those studies demonstrate that statins are well tolerated, safe an... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2971746 Fri, 06 Nov 2009 19:34:19 +0100 2971746 Scheie syndrome: Enzyme replacement therapy does not prevent progression of cervical myelopathy due to spinal cord compression http://www.medworm.com/index.php?rid=2971747&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu74x2630m1715826%2F We report a 38-year-old female Scheie patient who has been on ERT for 8 years. While non-neurological symptoms improved, she developed paresthesias in her hands and feet and progressive pain in her legs. Somatosensory evoked potentials were abnormal, suggesting dysfunction of the dorsal funiculus and lemniscus medialis. After 6 years of ERT, a spinal MRI showed dural thickening at the upper cervical spine. These soft-tissue deposits are presumably due to the accumulation of mucopolysaccharides. Intramedullary hyperintensities at the level of C1/2 revealed cervical myelopathy. An MRI before the start of ERT had shown milder spinal lesions. Cystic lesions in the white matter of the centrum semiovale due to dilated Virchow–Robin spaces were essentially unchanged compared wit... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2971747 Thu, 05 Nov 2009 18:42:04 +0100 2971747 Ear symptoms in children with Fabry disease: data from the Fabry Outcome Survey http://www.medworm.com/index.php?rid=2948156&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc4h8g50778356331%2F Conclusions: Hearing loss is a well-known clinical manifestation in patients with Fabry disease. It was reported in significant numbers of children in the FOS signs and symptoms questionnaire, but confirmed in only 19% by formal audiometry. The subjective hearing impairment may have been due to middle-ear effusions in many cases. Tinnitus is a well-recognized symptom in Fabry disease and can present in childhood. The presence of tinnitus correlated with overall disease severity. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10545-009-1290-xAuthors A. Keilmann, University Hospital Department for ENT and Communication Disorders Langenbeckstr. 1 55101 Mainz GermanyD. Hajioff, Southmead Hospital Department of Otolaryngology Bristol UKU. Ramaswami, Addenbrooke’s Un... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2948156 Fri, 30 Oct 2009 07:37:28 +0100 2948156 RFT1-CDG: Deafness as a novel feature of congenital disorders of glycosylation http://www.medworm.com/index.php?rid=2930067&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F12465889652u3844%2F Summary  Congenital disorders of glycosylation (CDG) are genetic diseases due to defects in the synthesis of glycans and in the attachment of glycans to lipids and proteins. Actually, some 42 CDG are known including defects in protein N-glycosylation, in protein O-glycosylation, in lipid glycosylation, and in multiple and other glycosylation pathways. Most CDG are multisystem diseases and a large number of signs and symptoms have already been reported in CDG. An exception to this is deafness. This symptom has not been observed as a consistent feature in CDG. In 2008, a novel defect was identified in protein N-glycosylation, namely in RFT1. This is a defect in the assembly of N-glycans. RFT1 is involved in the transfer of Man5GlcNAc2-PP-Dol from the cytoplasmic to the luminal... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2930067 Sat, 24 Oct 2009 07:55:20 +0100 2930067 Cognitive and social profiles in two patients with cobalamin C disease http://www.medworm.com/index.php?rid=2897685&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1g30776l86168170%2F Summary  Cobalamin C (cblC) disease, an inborn error of vitamin B12 metabolism, results in neurometabolic, neurochemical and neuroanatomical changes. Little is known of the long-term effects of the disorder on cognition and behaviour in children. Here, the complete neuropsychological profiles of two 12-year-old girls with cblC disease are presented. The two girls were tested longitudinally with standardized neuropsychological tests including intellectual ability, attention and memory, as well as executive, adaptive and behavioural function. The results indicate the presence of intellectual dysfunction, attention problems, and concerns with behavioural aspects of executive function. Both patients demonstrated a pattern of decreasing intellectual function over time, which may ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2897685 Wed, 14 Oct 2009 17:17:42 +0100 2897685 Novel mutation affecting the pterin-binding site of PTS gene and review of PTS mutations in Thai patients with 6-pyruvoyltetrahydropterin synthase deficiency http://www.medworm.com/index.php?rid=2897686&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0227503441l86032%2F In conclusion, severe neurological impairment from BH4 deficiency could be prevented by newborn screening for HPA and proper metabolic management. However, pterin analysis for early diagnosis of BH4 deficiency is still not available in most developing countries. Content Type Journal ArticleCategory CASE REPORTDOI 10.1007/s10545-009-1221-xAuthors N. Vatanavicharn, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangkoknoi Bangkok Thailand 10700C. Kuptanon, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangkoknoi Bangkok Thailand 10700S. Liammongkolkul, Faculty of Medicine Siriraj Hospital Division of Medical Genetics, Department of Pediatrics 2 Prannok Road, Bangko... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2897686 Wed, 14 Oct 2009 17:17:40 +0100 2897686 Development and implementation of a novel assay for l-2-hydroxyglutarate dehydrogenase (l-2-HGDH) in cell lysates: l-2-HGDH deficiency in 15 patients with l-2-hydroxyglutaric aciduria http://www.medworm.com/index.php?rid=2889435&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq57348h146555113%2F Summary   l-2-hydroxyglutaric aciduria (l-2-HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by mutations in the gene encoding l-2-hydroxyglutarate dehydrogenase. An assay to evaluate l-2-hydroxyglutarate dehydrogenase (l-2-HGDH) activity in fibroblast, lymphoblast and/or lymphocyte lysates has hitherto been unavailable. We developed an l-2-HGDH enzyme assay in cell lysates based on the conversion of stable-isotope-labelled l-2-hydroxyglutarate to 2-ketoglutarate, which is converted into l-glutamate in situ. The formation of stable isotope labelled l-glutamate is therefore a direct measure of l-2-HGDH activity, and this product is detected by liquid chromatography-tandem mass spectrometry. A deficiency of l-2-HGDH activity was detected in cell lysates ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889435 Sun, 11 Oct 2009 05:59:05 +0100 2889435 Clinical and biochemical studies in mucopolysaccharidosis type II carriers http://www.medworm.com/index.php?rid=2889437&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2r4366636551u54%2F Summary  The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16–57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels o... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889437 Sun, 11 Oct 2009 05:59:03 +0100 2889437 Hydroxocobalamin dose escalation improves metabolic control in cblC http://www.medworm.com/index.php?rid=2889436&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0p1605802xg70458%2F We describe the biochemical response of a 13-year-old boy with worsening metabolic parameters despite strict adherence to a conventional treatment regimen. We progressively increased the OHCbl dose from 1 to 20 mg IM per day and observed a dose-dependent response with an 80% reduction of plasma MMA (25 to 5.14 μmol/L; normal range <0.27 μmol/L), a 55% reduction of tHcy (112 to 50 μmol/L; normal range: 0–13 μmol/L) and a greater than twofold increase in methionine (17 to 36 μmol/L; normal range: 7–47 μmol/L). This suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients, but it is unknown whether it may slow or eliminate other complications. Future clinical trials to determine the ben... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889436 Sun, 11 Oct 2009 05:59:03 +0100 2889436 Mitochondria and diabetes mellitus: untangling a conflictive relationship? http://www.medworm.com/index.php?rid=2889440&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn8528t4275908715%2F Summary  Diabetes mellitus is occasionally observed in patients with skeletal muscle respiratory chain deficiency, suggesting that skeletal muscle mitochondrial dysfunction might play a pathogenic role in type 2 diabetes (T2D). In support of this hypothesis, decreased muscle mitochondrial activity has been reported in T2D patients and in mouse models of diabetes. However, recent work by several groups suggests that decreased muscle mitochondrial function may be a consequence rather than a cause of diabetes, since decreased mitochondrial function in mice affords protection from diabetes and obesity. We review the data on this controversial but important issue of potential links between mitochondrial dysfunction and diabetes. Content Type Journal ArticleCategory REVIEWDOI 1... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889440 Sun, 11 Oct 2009 05:59:02 +0100 2889440 Effort bruising disclosing Gaucher disease in a 55-year-old non-Jewish woman http://www.medworm.com/index.php?rid=2889439&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0j01270x11r22q8%2F Content Type Journal ArticleCategory IMAGES IN METABOLIC MEDICINEDOI 10.1007/s10545-009-1217-6Authors M. Machaczka, Karolinska University Hospital Huddinge Hematology Center Karolinska M54, SE-141 86 Stockholm SwedenM. Klimkowska, Karolinska University Hospital Huddinge Department of Pathology Stockholm SwedenH. Hägglund, Karolinska University Hospital Huddinge Hematology Center Karolinska M54, SE-141 86 Stockholm Sweden Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889439 Sun, 11 Oct 2009 05:59:02 +0100 2889439 Adult presentations of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) http://www.medworm.com/index.php?rid=2889438&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F73509022t7102h65%2F Summary  Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of mitochondrial fatty acid oxidation which is usually diagnosed in infancy or through neonatal screening. In the absence of population screening, adults with undiagnosed MCADD can be expected. This review discusses 14 cases that were identified during adulthood. The mortality of infantile patients is approximately 25% whereas in this adult case series it was shown it to be 50% in acutely presenting patients and 29% in total. Therefore, undiagnosed individuals are at risk of sudden fatal metabolic decompensation with high mortality. This review illustrates the need to consider the possibility of a fatty acid oxidation defect in an adult who presents with unexplained sudden cli... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2889438 Sun, 11 Oct 2009 05:59:02 +0100 2889438 Long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam] as a possible model to study renal disease in methylmalonic acidurias http://www.medworm.com/index.php?rid=2881034&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw2q71520373447t5%2F Summary  Dysfunction of proximal tubules resulting in tubulointerstitial nephritis and chronic renal failure is a frequent long-term complication of methylmalonic acidurias. However, the underlying pathomechanisms have not yet been extensively studied owing to the lack of suitable in vitro and in vivo models. Application of hydroxycobalamin[c-lactam] has been shown to inhibit the metabolism of hydroxycobalamin and, thereby, to induce methylmalonic aciduria in rats, oligodendrocytes, and rat hepatocytes. Our study characterizes the biochemical and bioenergetic effects of long-term exposure of human proximal tubule cells to hydroxycobalamin[c-lactam], aiming to establish a novel in vitro model for the renal pathogenesis of methylmalonic acidurias. Incubation of human proximal ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2881034 Fri, 09 Oct 2009 06:24:36 +0100 2881034 Pathophysiology of fatty acid oxidation disorders http://www.medworm.com/index.php?rid=2881036&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv2718x571843u821%2F This article provides an overview of the pathogenesis of fatty acid oxidation disorders. It describes the different tissue involvement with the disease processes and correlates disease phenotype with the nature of the genetic defect for the known disorders of the pathway. Content Type Journal ArticleCategory Fatty Acid OxidationDOI 10.1007/s10545-009-1294-6Authors M. J. Bennett, University of Pennsylvania and Children’s Hospital of Philadelphia Department of Pathology & Laboratory Medicine 34th Street & Civic Center Blvd, 5NW58 Philadelphia PA 19104 USA Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2881036 Fri, 09 Oct 2009 06:24:34 +0100 2881036 Remarkable differences: the course of life of young adults with galactosaemia and PKU http://www.medworm.com/index.php?rid=2881035&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5244g8381tm85155%2F This study investigated the CoL and the social demographical outcomes in these young adults with galactosaemia, and compared them with the general population and with PKU patients. A total of 15 (88%) adult patients with classical galactosaemia participated in this study. Classical galactosaemia patients had a delayed social and psychosexual development compared to their peers from the general population and to PKU patients. Also, they were significantly less frequently married or living together and significantly less frequently employed than the general population. Our study shows a stark contrast between patients with galactosaemia and patients with PKU, although both are diagnosed in the neonatal period and need life-long dietary restrictions. The observed difference is likely du... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2881035 Fri, 09 Oct 2009 06:24:34 +0100 2881035 Secondary disorders of glycosylation in inborn errors of fructose metabolism http://www.medworm.com/index.php?rid=2818203&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr676340002661121%2F We describe a girl with neonatal hypertonia, facial trismus, absent swallowing and coughing reflexes, gastro-oesophageal reflux and sporadically elevated Krebs cycle metabolites and lactate. At 14 months microcephaly and hepatomegaly were noted, with hypertransaminasaemia but normal blood coagulation, glucose, phosphate, and absent urinary reducing substances. Neurological impairment persisted. Because of hepatic and neurological abnormalities with developmental delay, Tf IEF was performed and showed a severe type 1 pattern, resulting in a wrong diagnosis of CDG. Subsequently, an aversion to fruits suggested HFI, confirmed by the finding of ALDOB mutations (p.A150P/p.N335K). The girl improved with fructose-free diet, but liver cirrhosis led to hepatic transplantation. She is now... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2818203 Sun, 20 Sep 2009 05:36:19 +0100 2818203 Prevalence of classical phenylketonuria in mentally retarded individuals in Iran http://www.medworm.com/index.php?rid=2811984&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F041083011011pr85%2F Summary  Using Guthrie Biological Inhibition Assay, 4963 mentally retarded individuals housed in 31 cities and towns across the country were screened for PKU. The average prevalence of classical PKU in the study population was 2.1%, which is higher than that reported for most mentally retarded populations in other countries prior to the implementation of a nationwide newborn screening programme for PKU. The prevalence of PKU in 1814 mentally retarded inmates housed in shelters in Tehran was 2.81%, and the prevalence of the disease in 3149 inmates sheltered in other cities and towns was 1.68%. It appears that most of the difference between the prevalence of PKU in these two populations is due to a unique PKU referral pattern in Iran. The high prevalence of PKU in the mentall... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811984 Fri, 18 Sep 2009 16:27:21 +0100 2811984 Neurometabolic disorders http://www.medworm.com/index.php?rid=2811985&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftk06337834754672%2F Content Type Journal ArticleCategory EDITORIALDOI 10.1007/s10545-009-9958-9Authors Jean-Marie Saudubray, Assistance Publique Hôpitaux de Paris et Université Pierre et Marie Curie (Paris VI) Departement des maladies métaboliques, Federation des maladies du système nerveux Hôpital Pitié-Salpêtrière Paris France Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811985 Wed, 16 Sep 2009 13:15:01 +0100 2811985 High incidence of profound biotinidase deficiency detected in newborn screening blood spots in the Somalian population in Minnesota http://www.medworm.com/index.php?rid=2811987&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr7815549w7728174%2F Summary  Newborns identified with profound biotinidase deficiency (BTD) by the Minnesota Newborn Screening Program (MN NBS) between 1 October 2004 and 30 May 2008 were all from new immigrant groups. Thirty-three positive cases of BTD were identified out of 264 727 infants screened by the Wolf colorimetric system during the period of this study by MN NBS. Five cases of profound BTD (0.1 to <0.6 nmol/min per ml) and 26 cases of partial BTD (0.9 to 2.3 nmol/min per ml) were later confirmed through measurement of serum biotinidase activity. The incidence of combined partial and profound BTD of 1/8540 and that of profound BTD of 1/52 945 in Minnesota are unusually high in comparison with the reported worldwide numbers of 1/61 067 for combined BTD and 1/137 401 for p... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811987 Wed, 16 Sep 2009 13:15:00 +0100 2811987 Retinal detachment causing unilateral blindness in a 12-year-old girl with gyrate atrophy http://www.medworm.com/index.php?rid=2811986&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F26xgmn06871q56t4%2F Content Type Journal ArticleCategory IMAGES IN METABOLIC MEDICINEDOI 10.1007/s10545-009-1220-yAuthors C. P. Barnett, Division of Ophthalmology, The Hospital for Sick Children Division of Clinical and Metabolic Genetics 555 University Ave Toronto Ontario Canada M5G 1X8W.-C. Lam, Division of Ophthalmology, The Hospital for Sick Children Division of Clinical and Metabolic Genetics 555 University Ave Toronto Ontario Canada M5G 1X8A. Schulze, Division of Ophthalmology, The Hospital for Sick Children Division of Clinical and Metabolic Genetics 555 University Ave Toronto Ontario Canada M5G 1X8 Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811986 Wed, 16 Sep 2009 13:15:00 +0100 2811986 Inborn errors of metabolism and motor disturbances in children http://www.medworm.com/index.php?rid=2811988&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F91027j732hq17641%2F Summary  Motor disturbances are very common in paediatric neurology. Often families can be reassured that these are just variants of normal development. However, abnormal movements can also be the hallmark of severe brain dysfunction of different and complex origins. This review concentrates on motor disturbances as frequent and important symptoms of inborn errors of metabolism. A structured diagnostic approach is developed taking into account age-dependent physiological developments and pathophysiological responses of gross and fine motor functions. A series of investigations are presented with the primary aim of early diagnosis of treatable conditions. The correct recognition and differentiation of movement disorders (ataxia, rigid akinetic syndrome (‘parkinsonism’), ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811988 Wed, 16 Sep 2009 13:14:58 +0100 2811988 Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review http://www.medworm.com/index.php?rid=2811989&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq2h1101233t20770%2F Summary  The congenital disorders of glycosylation (CDG) are a recently described group of inherited multisystem disorders characterized by defects predominantly of N- and O-glycosylation of proteins. Cardiomyopathy in CDG has previously been described in several subtypes; it is usually associated with high morbidity and mortality and the majority of cases present in the first 2 years of life. This is the first case with presentation in late childhood and the article reviews current literature. An 11-year-old female with a background of learning difficulties presented in cardiac failure secondary to severe dilated cardiomyopathy. Prior to the diagnosis of CDG, her condition deteriorated; she required mechanical support (Excor Berlin Heart) and was listed for cardiac tra... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2811989 Wed, 16 Sep 2009 13:14:56 +0100 2811989 Diagnosis, treatment, follow-up and gene mutation analysis in four Chinese children with biotinidase deficiency http://www.medworm.com/index.php?rid=2768088&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F644004t24118x637%2F Conclusions: Early recognition of biotinidase deficiency is crucial to avoid permanent damage. Determination of biotinidase activity should be included in neonatal screening in China. Exon 4 may be a hot-spot for biotinidase gene mutations in Chinese patients. Four novel gene variations may be disease-causing mutations and should be confirmed by expression studies. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1238-1Authors J. Ye, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research Department of Pediatric Endocrinology and Genetic Metabolism, Xin Hua Hospital 1665 Kong Jiang Road Shanghai 200092 ChinaT. Wang, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research Department of Pedi... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2768088 Thu, 03 Sep 2009 06:41:28 +0100 2768088 Diagnosis of glutathione synthetase deficiency in newborn screening http://www.medworm.com/index.php?rid=2768087&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fep4p57h586u33754%2F Summary  Glutathione synthetase (GSS) deficiency is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with haemolytic anaemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low GSS activity in erythrocytes or cultured skin fibroblasts. Diagnosis can be confirmed by mutational analysis. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. The most important determinants for outcome and survival in patients with GSS deficiency are early diagnosis and early initiation of treatment. The case of a newborn with GSS deficiency diagnosed by tandem m... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2768087 Thu, 03 Sep 2009 06:41:28 +0100 2768087 Total oxidant-scavenging capacities of plasma from glycogen storage disease type Ia patients as measured by cyclic voltammetry, FRAP and luminescence techniques http://www.medworm.com/index.php?rid=2768089&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw0v757l1w803j050%2F Summary  It has been suggested that the very low incidence of atherosclerosis in glycogen storage disease type Ia (GSD Ia) subjects might be attributed to elevated levels of uric acid, one of the potent low-molecular-weight antioxidants found in plasma. The present communication describes a use of two analytical methods—cyclic voltammetry and ferric reducing ability of plasma—and also two chemiluminescence methods to evaluate the total oxidant-scavenging capacities (TOSC) of plasma from GSD Ia patients. Our results verified the elevation of TOSC in GSD Ia patients and we propose the inclusion of luminescence and cyclic voltammetry assays as reliable methods for estimating TOSC in a variety of clinical disorders. Our findings with the cyclic voltammetry method add suppor... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2768089 Thu, 03 Sep 2009 06:41:27 +0100 2768089 Insidious peripheral neuropathy occurring under treatment in infantile MTHFR deficiency http://www.medworm.com/index.php?rid=2724084&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqr783079v0731516%2F Summary  5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency was diagnosed in a 1-month-old baby with signs of cerebral distress. Under a classic treatment using methionine supplementation, methyl donor (betaine) folinic acid, vitamin B6 and vitamin B12, the neuromotor development was satisfactory. At 15 years of age, however, despite no clear modification of the biochemical markers in body fluids, she developed a clinically overt peripheral axonal neuropathy. Only partial clinical improvement was obtained after reinforcement of betaine doses. Surveillance of the peripheral nerve is indicated in MTHFR deficiency, including in the infantile form with a good therapeutic compliance. Content Type Journal ArticleCategory Short ReportDOI 10.1007/s10545-009-1240-7Aut... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2724084 Thu, 20 Aug 2009 19:58:03 +0100 2724084 A new case of ALG8 deficiency (CDG Ih) http://www.medworm.com/index.php?rid=2715015&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhv4333371176n6q4%2F Conclusion: The prognosis of patients with ALG8 deficiency is unfavourable. The majority of affected children have early onset of the disease with heterogeneous symptoms including multiple organ dysfunction, coagulopathy and protein-losing enteropathy. Neurological impairment is not a general clinical symptom, but it has to be taken into consideration when thinking about ALG8 deficiency. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1203-zAuthors K. Vesela, Charles University Department of Pediatrics, First Faculty of Medicine Ke Karlovu 2 128 08 Prague 2 Czech RepublicT. Honzik, Charles University Department of Pediatrics, First Faculty of Medicine Ke Karlovu 2 128 08 Prague 2 Czech RepublicH. Hansikova, Charles University Department of Pediatrics, First F... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2715015 Tue, 18 Aug 2009 08:26:41 +0100 2715015 Glyceryl triacetate for Canavan disease: A low-dose trial in infants and evaluation of a higher dose for toxicity in the tremor rat model http://www.medworm.com/index.php?rid=2707948&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp22j531r85307636%2F Summary  Canavan disease (CD) is a fatal dysmyelinating genetic disorder associated with aspartoacylase deficiency, resulting in decreased brain acetate levels and reduced myelin lipid synthesis in the developing brain. Here we tested tolerability of a potent acetate precursor, glyceryl triacetate (GTA), at low doses in two infants diagnosed with CD, aged 8 and 13 months. Much higher doses of GTA were evaluated for toxicity in the tremor rat model of CD. GTA was given orally to the infants for up to 4.5 and 6 months, starting at 25 mg/kg twice daily, doubling the dose weekly until a maximum of 250 mg/kg reached. Wild-type and tremor rat pups were given GTA orally twice daily, initially at a dose of 4.2 g/kg from postnatal days 7 through 14, and at 5.... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2707948 Fri, 14 Aug 2009 16:54:47 +0100 2707948 Mental retardation and inborn errors of metabolism http://www.medworm.com/index.php?rid=2707947&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0r210504323628x2%2F Summary  In countries where clinical phenylketonuria is detected by newborn screening inborn errors of metabolism are rare causes of isolated mental retardation. There is no international agreement about what type of metabolic tests must be applied in patients with unspecific mental retardation. However, and although infrequent, there are a number of inborn errors of metabolism that can present in this way. Because of the high recurrence risk and the possibility of specific therapies, guidelines need to be developed and adapted to different populations. The application of a universal protocol may result in a low diagnostic performance in individual ethnic populations. Consideration of associated signs (extraneurological manifestations, psychiatric signs, autistic traits, ce... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2707947 Fri, 14 Aug 2009 16:54:47 +0100 2707947 Management of neuronopathic Gaucher disease: Revised recommendations http://www.medworm.com/index.php?rid=2680948&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk0053551261l9n07%2F Summary  The original guidelines drawn up for the management of the neuronopathic forms of Gaucher disease were felt to be in need of revision; in particular, the role of high-dose enzyme replacement therapy (120 IU/kg of body weight every 2 weeks) in stabilizing neurological disease. The existing published evidence was analysed; it was concluded that it did not support the role of high-dose ERT, although this might be required to treat severe visceral disease. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-1164-2Authors A. Vellodi, Metabolic Unit, Great Ormond Street Hospital for Children NHS Trust Great Ormond Street WC1N 3JH London UKA. Tylki-Szymanska, The Children’s Memorial Health Institute Warsaw PolandE. H. Davies, Institute of ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2680948 Tue, 04 Aug 2009 21:36:05 +0100 2680948 Epilepsy and inborn errors of metabolism in children http://www.medworm.com/index.php?rid=2662226&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F17401027x53117nt%2F Summary  Epilepsy is a frequent symptom in inborn errors of metabolism, with virtually no specific seizure types or EEG signatures. It is most important to look quickly for those few inborn errors of metabolism in which specific therapies such as supplementation of cofactors or diets can make all the difference. If these investigations remain negative, epilepsy has to be treated with conventional antiepileptic drugs. Still, epilepsy is a potentially treatable symptom of many inborn errors of metabolism, and optimal treatment is of great importance for patients and their families. Content Type Journal ArticleCategory REVIEWDOI 10.1007/s10545-009-1171-3Authors N. I. Wolf, VU University Medical Center (VUMC) Department of Child Neurology Postbus 7057 1007 MB Amsterdam The N... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2662226 Thu, 30 Jul 2009 07:49:46 +0100 2662226 Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters http://www.medworm.com/index.php?rid=2662227&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg55r0888j4084103%2F Conclusion Outcome in MMAurias is best predicted by the enzymatic subgroup, cobalamin responsiveness, age at onset and birth decade. The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut0 patients. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-1189-6Authors F. Hörster, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 430 D-69120 Heidelberg GermanyS. F. Garbade, University Children’s Hospital Heidelberg Department of General Pediatrics, Division of Inborn Metabolic Diseases Im Neuenheimer Feld 430 D-69120 Heidelberg GermanyT. Zwickler, University Children’s Hospital Heidelberg Departme... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2662227 Thu, 30 Jul 2009 07:49:42 +0100 2662227 A cognitively normal PDH-deficient 18-year-old man carrying the R263G mutation in the PDHA1 gene http://www.medworm.com/index.php?rid=2662228&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwh8164tp1n0g7r7n%2F We report a case with a previously known common mutation in PDHA1 (R263G) with an excellent outcome at 18 years of age. Previous patients with this mutation have presented with mental retardation and/or Leigh syndrome, while our patient’s clinical outcome is exceptional. He is cognitively normal and has normal brain MRI. His management includes a stringent carbohydrate-free diet, as well as supplementation with thiamine, carnitine and vitamin E. This case further broadens the clinical spectrum, including now an example of a cognitively normal adult with PDH deficiency. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1101-4Authors R. Bachmann-Gagescu, University of Washington School of Medicine Division of Medical Genetics, Department of Medicine Seat... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2662228 Wed, 29 Jul 2009 07:01:10 +0100 2662228 Long-term needs of adult patients with organic acidaemias: outcome and prognostic factors http://www.medworm.com/index.php?rid=2644183&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm5h2r7362m776428%2F Conclusions: The approach to adult patients with OA has to be multidisciplinary, with the clinician and dietician as the core of the team, but with the collaboration of clinical nurses specialists, social workers and other specialist services and the support of a biochemical and molecular laboratory. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-1191-12Authors E. Martín-Hernández, UCLH Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery London UKP. J. Lee, UCLH Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery London UKA. Micciche, UCLH Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery London UKS. Grunewald, Great Ormond Street Hospital, UCL Department for Metabolic Medi... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2644183 Sat, 25 Jul 2009 04:33:59 +0100 2644183 Metabolic phenotypes of phenylketonuria. Kinetic and molecular evaluation of the Blaskovics protein loading test http://www.medworm.com/index.php?rid=2633239&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr637nn8681v0845w%2F Summary   Background: As part of the German Collaborative Study of Children Treated for Phenylketonuria (PKU), a three-day protein loading test was applied to children at 6 months of age. This load elicits three principal types of blood phenylalanine (Phe) response, with types I and III clinically corresponding to classic PKU and mild hyperphenylalaninaemia not requiring diet (MHP), respectively. An intermediate type II, clinically corresponding to mild PKU, is characterized by early decline of blood Phe from above 1200 μmol/L down to levels between 600 and 1200 μmol/L at 72 h. Aims: Unbiased classification and kinetic and molecular characterization of the intermediate Phe response; estimation of phenotypic variability of Phe disposal.Method: A kinetic model wit... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2633239 Tue, 21 Jul 2009 00:09:00 +0100 2633239 In response to van Spronsen et al (2009) Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU (J Inherit Metab Dis 32: 27–31) http://www.medworm.com/index.php?rid=3099277&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhht7348v17746462%2F In response to van Spronsen et al (2009) Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU (J Inherit Metab Dis 32: 27–31) Content Type Journal ArticleCategory LETTER TO THE EDITORDOI 10.1007/s10545-009-9959-8Authors Alberto Ponzone, University of Torino Department of Pediatrics Torino ItalyAlessandro Mussa, University of Torino Department of Pediatrics Torino ItalyFrancesco Porta, University of Torino Department of Pediatrics Torino Italy Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 Journal Volume Volume 32 Journal Issue Volume 32, Number 4 / August, 2009 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=3099277 Tue, 21 Jul 2009 00:08:59 +0100 3099277 In response to van Spronsen et al (2009) Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU (J Inherit Metab Dis 32: 27–31) http://www.medworm.com/index.php?rid=2633241&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhht7348v17746462%2F Content Type Journal ArticleCategory LETTER TO THE EDITORDOI 10.1007/s10545-009-9959-8Authors Alberto Ponzone, University of Torino Department of Pediatrics Torino ItalyAlessandro Mussa, University of Torino Department of Pediatrics Torino ItalyFrancesco Porta, University of Torino Department of Pediatrics Torino Italy Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2633241 Tue, 21 Jul 2009 00:08:59 +0100 2633241 Gender dimorphism in siblings with schizophrenia-like psychosis due to Niemann-Pick disease type C http://www.medworm.com/index.php?rid=2633240&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2p25385q66n1j854%2F We describe the differential presentation of schizophrenia-like psychosis in two siblings with the ‘variant’ biochemical presentation of adult Niemann-Pick disease type C. The male sibling presented with psychosis at age 16 years and cognitive and motor disturbance at age 25 years, whereas his elder sister, sharing the same mutation but showing less severe biochemical, neuroimaging and ocular motor parameters, presented with a similar schizophrenia-like illness with associated cognitive and motor disturbance at age 31 years. Their illness onset, course and response to treatment mirrors the sex dimorphism seen in schizophrenia, and is suggestive of an interaction between the neurobiology of their metabolic disorder and sex differences in neurodevelopment. Content ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2633240 Tue, 21 Jul 2009 00:08:59 +0100 2633240 Mortality and cause of death in mucopolysaccharidosis type II—a historical review based on data from the Hunter Outcome Survey (HOS) http://www.medworm.com/index.php?rid=2605001&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgw6480557024x034%2F Summary  Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a progressive, multisystemic disease caused by a deficiency of iduronate-2-sulfatase. Patients with the severe form of the disease have cognitive impairment and typically die in the second decade of life. Patients with the less severe form do not experience significant cognitive involvement and may survive until the fifth or sixth decade of life. We studied the relationship of both severity of MPS II and the time period in which patients died with age at death in 129 patients for whom data were entered retrospectively into HOS (Hunter Outcome Survey), the only large-scale, multinational observational study of patients with MPS II. Median age at death was significantly lower in patients with cognitive invo... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2605001 Tue, 14 Jul 2009 11:09:34 +0100 2605001 Inherited disorders in the conversion of methionine to homocysteine http://www.medworm.com/index.php?rid=2592839&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk53w2j6324884p1n%2F Summary  During the last decade much important new information relating to the metabolic pathway from methionine to homocysteine has been gained. Interest has been stimulated by the discovery of two novel disorders, glycine N-methyltransferase deficiency and S-adenosylhomocysteine hydrolase deficiency. Another disorder in this pathway, methionine adenosyltransferase deficiency, has been increasingly detected, thanks to the expansion of newborn screening programmes by tandem mass spectrometry technology. These significant steps allow important insight into the pathogenesis of these three disorders, as well as into the mechanisms of damage to various organs (liver, brain, muscle) and point to the relevance of these disorders for crucial biological processes such as methylation... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592839 Thu, 09 Jul 2009 12:32:56 +0100 2592839 Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias http://www.medworm.com/index.php?rid=2592841&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjm70269207h8n335%2F Conclusion: Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias is probably a marker of a serious disease. One patient with this complication survived after a strong reduction of glucose administration. Even if this is probably only a partial intervention, we hypothesize that in this situation a reduction of glucose administration can reduce almost the risk of persistent hyperglycaemia. Further studies are required to confirm our hypothesis. Content Type Journal ArticleCategory ONLINE REPORTDOI 10.1007/s10545-009-1141-9Authors L. Filippi, ‘A. Meyer’ University Children’s Hospital Neonatal Intensive Care Unit, Department of Critical Care Medicine viale Pieraccini, 24 50134 Florence ItalyE. Gozzini, ‘A. Meyer’ University Ch... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592841 Thu, 09 Jul 2009 12:32:54 +0100 2592841 Serum phenylalanine concentrations in patients post trauma and burn correlate to neopterin concentrations http://www.medworm.com/index.php?rid=2592840&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft0553028m5203781%2F Content Type Journal ArticleCategory LETTER TO THE EDITORDOI 10.1007/s10545-009-9960-2Authors S. Scholl-Buergi, Biocenter, Innsbruck Medical University Department of Pediatrics Innsbruck AustriaG. Neurauter, Innsbruck Medical University Division of Biological Chemistry, Biocenter Fritz Pregl Strasse 3 6020 Innsbruck AustriaD. Karall, Biocenter, Innsbruck Medical University Department of Pediatrics Innsbruck AustriaD. Fuchs, Innsbruck Medical University Division of Biological Chemistry, Biocenter Fritz Pregl Strasse 3 6020 Innsbruck Austria Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592840 Thu, 09 Jul 2009 12:32:54 +0100 2592840 Retinitis pigmentosa and mucopolysaccharidosis type II: an extremely attenuated phenotype http://www.medworm.com/index.php?rid=2592842&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F202613115662p3x7%2F Content Type Journal ArticleCategory IMAGES IN METABOLIC MEDICINEDOI 10.1007/s10545-009-1204-yAuthors Y. Suzuki, Gifu University Graduate School of Medicine Department of Pediatrics and Medical Education Development Center Yanagido 1-1 Gifu 501-1194 JapanA. Aoyama, Gifu University Graduate School of Medicine Department of Ophthalmology Gifu JapanT. Kato, Gifu University Graduate School of Medicine Department of Pediatrics and Medical Education Development Center Yanagido 1-1 Gifu 501-1194 JapanN. Shimozawa, Gifu University Division of Genomic Research, Life Science Research Center Gifu JapanT. Orii, Orii Clinic Gifu Japan Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592842 Thu, 09 Jul 2009 12:32:52 +0100 2592842 Experience with the treatment of argininosuccinic aciduria during pregnancy http://www.medworm.com/index.php?rid=2592843&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9661l72635611115%2F We present the details of the management and the outcome of a pregnancy of a woman affected with argininosuccinic aciduria. Management with a closely monitored, protein-restricted diet, supplemented with L-arginine, resulted in the birth of a healthy infant boy and an uneventful perinatal course for the mother. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1145-5Authors L. Reid, Centre hospitalier universitaire de Sherbrooke Service de génétique médicale 3001, 12th Avenue Nord Sherbrooke Québec J1H 5N4 CanadaÉ. Perreault, Centre hospitalier universitaire de Sherbrooke Service de génétique médicale 3001, 12th Avenue Nord Sherbrooke Québec J1H 5N4 CanadaG. Lafrance, Centre hospitalier universitaire de Sherbrooke Service de génétique médicale 3001,... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592843 Thu, 09 Jul 2009 12:32:51 +0100 2592843 Danon disease: Case report and detection of new mutation http://www.medworm.com/index.php?rid=2592844&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1mp4173123804r30%2F We report a male patient with skeletal myopathy, mental retardation, and massive hypertrophic obstructive cardiomyopathy necessitating heart transplantation. Immunohistochemistry of skeletal muscle and leukocytes, western blot analysis of leukocytes and cardiac muscle, flow cytometry, and DNA sequencing were performed. Muscle biopsy revealed autophagic vacuolar myopathy and lack of immunohistochemically detectable LAMP-2. Diagnosis of Danon disease was confirmed by western blot analysis of myocardial tissue and peripheral blood sample of the patient showing deficiency of LAMP-2 in myocardium and leukocytes. Moreover, absence of LAMP-2 in lymphocytes, monocytes and granulocytes was shown by flow cytometric analysis. Genetic analysis of the LAMP2 gene revealed a novel 1-bp deletion at ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2592844 Thu, 09 Jul 2009 12:32:50 +0100 2592844 Sleep-related breathing in children with mucopolysaccharidosis http://www.medworm.com/index.php?rid=2559434&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg332710767w83563%2F Conclusions: Children with MPS have a high prevalence of significant OSA and thus should be carefully screened for OSA using full polysomnography and treated accordingly. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10545-009-1170-4Authors A. Nashed, The Hospital for Sick Children Toronto Ontario CanadaS. Al-Saleh, The Hospital for Sick Children Toronto Ontario CanadaJ. Gibbons, The Hospital for Sick Children Toronto Ontario CanadaI. MacLusky, The Children’s Hospital of Eastern Ontario Ottawa Ontario CanadaJ. MacFarlane, University of Toronto Department of Paediatrics and Psychiatry Toronto Ontario CanadaA. Riekstins, The Hospital for Sick Children Toronto Ontario CanadaJ. Clarke, The Hospital for Sick Children Toronto Ontario CanadaI. Narang, The Hospital for ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2559434 Mon, 29 Jun 2009 08:24:13 +0100 2559434 Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs http://www.medworm.com/index.php?rid=2559435&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0250912230732ng1%2F Summary  Intravenous enzyme replacement therapy with recombinant human α-l-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase leve... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2559435 Mon, 29 Jun 2009 08:24:07 +0100 2559435 Orotic aciduria and uridine monophosphate synthase: A reappraisal http://www.medworm.com/index.php?rid=2559436&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy27741337300r42h%2F Abstract  Three subtypes of hereditary orotic aciduria are described in the literature, all related to deficiencies in uridine monophosphate synthase, the multifunctional enzyme that contains both orotate: pyrophosphoryl transferase and orotidine monophosphate decarboxylase activities. The type of enzyme defect present in the subtypes has been re-examined by steady-state modelling of the relative outputs of the three enzymic products, uridine monophosphate, urinary orotic acid and urinary orotidine. It is shown that the ratio of urinary outputs of orotidine to orotate provides a means of testing for particular forms of enzyme defect. It is confirmed that the type I defect is caused by loss of uridine monophosphate synthase activity. Cells and tissue of type I cases have a r... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2559436 Mon, 29 Jun 2009 08:24:00 +0100 2559436 IgM monoclonal component associated with type I Gaucher disease resolved after enzyme replacement therapy: A case report http://www.medworm.com/index.php?rid=2559437&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp414491427m65k28%2F We present the case of a 65-year-old woman with extensive GD I associated with IgM MGUS, in whom enzyme replacement therapy succeeded in eradicating the monoclonal component. This observation further supports the idea that enzyme replacement therapy decreases the chronic antigenic stimulation responsible for gammopathies in Gaucher disease. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-1207-8Authors C. Martinez-Redondo, Hospital Universitario J.M. Morales Meseguer Hematology and Clinical Oncology Unit Marqués de los Vélez s/n 30008 Murcia SpainF. J. Ortuño, Hospital Universitario J.M. Morales Meseguer Hematology and Clinical Oncology Unit Marqués de los Vélez s/n 30008 Murcia SpainM. L. Lozano, Hospital Universitario J.M. Morales Meseguer Hematolo... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2559437 Mon, 29 Jun 2009 08:23:52 +0100 2559437 Long-term neurodevelopmental effects of early detection and treatment in a 6-year-old patient with argininaemia diagnosed by newborn screening http://www.medworm.com/index.php?rid=2559438&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff74767u337l14r8u%2F Summary  Newborn screening makes possible the early identification and treatment of asymptomatic ARG1-deficient patients; however, it is unknown whether early intervention prevents neurological insults. We identified a full-term Hispanic male infant with argininaemia by newborn screening with a serum arginine of 327 µmol/L (reference values 0–140); ARG1 was undetectable on enzyme assay. Sequence analysis of ARG1 revealed a heterozygous nonsense mutation, c.223A>T (p.K75X), and a novel heterozygous missense variant, c.425G>A (p.G142E). Dietary protein restriction began from age 3 months, with addition of sodium benzoate at 4 months, and carnitine from 14 months. For the past 6 years, his serum arginine concentrations were maintained between 2... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2559438 Mon, 29 Jun 2009 08:23:45 +0100 2559438 Preface http://www.medworm.com/index.php?rid=2549964&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcq8218012u724227%2F Content Type Journal ArticleDOI 10.1007/BF03047364Authors G. M. AddisonR. A. ChalmersR. J. PollitP. DivryR. A. Harkness Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 Journal Volume Volume 7 Journal Issue Volume 7, Supplement 1 / March, 1984 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549964 Fri, 26 Jun 2009 06:29:37 +0100 2549964 The differential diagnosis of dicarboxylic aciduria http://www.medworm.com/index.php?rid=2549965&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu1317nu7vq448x85%2F Abstract  Various types of dicarboxylic aciduria are known, most of them are accompanied by non-ketotic hypoglycaemia. For the differential diagnosis of these conditions several methods of investigation have been used: (1) analysis of urinary organic acids in both native and hydrolysed samples, (2) analysis of free and esterified carnitine, the latter by means of chromatographic separation and identification of acyl moieties, (3) analysis of plasma organic acids, including the so-called free fatty acids, (4) a prolonged fasting test with serial measurements of the aforementioned parameters and close monitoring of the blood glucose and (5) an oral loading test with medium chain triglycerides accompanied by the same measurements as those named in item (4). So far differenti... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549965 Fri, 26 Jun 2009 06:29:31 +0100 2549965 Gas chromatography-mass spectrometry (GC-MS) diagnosis of two cases of medium chain Acyl-CoA dehydrogenase deficiency http://www.medworm.com/index.php?rid=2549966&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb158300200j45436%2F Abstract  Two patients with hypoketotic hypoglycaemia and dicarboxylic aciduria are described. Studies of their urinary organic acids by gas chromatography-mass spectrometry (GC-MS) showed an excretion of dicarboxylic acids (adipic suberic and sebacic acids), unsaturated dicarboxylic acids (cis-octenedioic and decenedioic acids), 5-hydroxyhexanoic acid, hexanoyl-glycine and suberylglycine. Deficiency of the medium chain acyl-CoA dehydrogenase (MCAD) in fibroblasts was documented for both children. Despite a similar presentation (hypoglycaemic coma), organic acid profile (dicarboxylic aciduria and suberylglycine excretion) and enzyme deficiency (MCAD), they did not respond similarly to glucose infusion. Content Type Journal ArticleCategory Dicarboxylic Acidurias And Acyl-C... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549966 Fri, 26 Jun 2009 06:29:24 +0100 2549966 Carnitine metabolism and inborn errors http://www.medworm.com/index.php?rid=2549967&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft4l85847r8h46249%2F Abstract  Current knowledge of the metabolic role, biosynthesis, cellular uptake, excretion and turnover of carnitine is reviewed. The clinical spectrum and possible aetiology of the primary muscle and primary systemic carnitine deficiency syndromes are considered and the various genetic defects of intermediary metabolism which can give rise to secondary carnitine deficiency are indicated. Content Type Journal ArticleCategory Dicarboxylic Acidurias And Acyl-Coa Dehydrogenase DeficienciesDOI 10.1007/BF03047372Authors A. G. Engel, Mayo Clinic and Mayo Foundation Neuromuscular Research Laboratory, Department of Neurology 55905 Rochester MN USAC. J. Rebouche, Mayo Clinic and Mayo Foundation Neuromuscular Research Laboratory, Department of Neurology 55905 Rochester MN USA ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549967 Fri, 26 Jun 2009 06:29:18 +0100 2549967 Long term outcome of organic acidurias: Survey of 105 French cases (1967–1983) http://www.medworm.com/index.php?rid=2549968&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa4501612q2222144%2F Abstract  The French experience in the long term follow-up of 105 cases of organic aciduria (45 maple syrup urine disease, 12 isovaleric acidaemia, 19 propionic acidaemia, 24 methylmalonic aciduria and some rare allied disorders) is reported. Main conclusions drawn from this survey are the poor overall prognosis and the slow improvement in the outcome of such disorders over the last 15 years. In MSUD, while early diagnosis and early management remain a basic requirement, intellectual development did not improve as much as expected. In propionic and methylmalonic acidaemia modern treatment does not prevent a fatal outcome in the classical neonatal forms. It should be also emphasized that in the rare cases where a coenzyme deficiency has been demonstrated, vitamin therapy is ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549968 Fri, 26 Jun 2009 06:29:11 +0100 2549968 Hudson memorial lecture http://www.medworm.com/index.php?rid=2549969&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr254480685190150%2F Abstract  Therapeutic guidelines have been obtained from a restrospective review of 41 patients affected with organic acidaemias, 16 patients with neonatal maple syrup urine disease (MSUD), 11 methylmalonic acidaemia, (MMA) seven propionic acidaemias (PA) and seven isovaleric acidaemias (IVA), and by comparing this personal series with similar reported cases. The emergency treatment of these organic acidurias in the neonate has to main goals: toxin removal and anabolism. Anabolism is always promoted by early diet therapy. The best method of toxin removal depends on the nature of the defect; peritoneal dialysis with exchange transfusions or multiple or prolonged exchange transfusions in MSUD and in PA, diuresis and exchange transfusions in MMA and glycine supplementation in ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549969 Fri, 26 Jun 2009 06:29:04 +0100 2549969 Glutaric acidaemia type II (multiple Acyl-Coa dehydrogenation deficiency) http://www.medworm.com/index.php?rid=2549970&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9438t53177513q22%2F Abstract  The clinical and biochemical phenotype of glutaric acidaemia type II (GAII) has led to the suggestion that the defect in the disorder affects electron transfer from primary FAD-containing dehydrogenases into the respiratory chain. Two proteins are involved in this process, i.e. electron transfer flavoprotein (ETF) and ETF dehydrogenase, an iron-sulphur flavoprotein with a distinctive EPR signal. Reliable catalytic assays for these proteins are not available, but both proteins have been purified and antisera against them prepared in rabbits. SDS-PAG electrophoresis of liver mitochondrial membranes from a GAII infant with congenital anomalies, locating ETF dehydrogenase with specific antiserum, showed no cross-reactive material. EPR of the same membranes showed a ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549970 Fri, 26 Jun 2009 06:28:58 +0100 2549970 Fatty Acyl-CoA dehydrogenase deficiency: Enzyme measurement and studies on alternative metabolism http://www.medworm.com/index.php?rid=2549971&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq071074m16q07334%2F Abstact  Fatty acyl-CoA dehydrogenase deficiencies are defined as disorders of the metabolism of straight chain acyl-CoA esters at the level of short chain acyl-CoA, general (medium chain) acyl-CoA and long chain acyl-CoA dehydrogenases. Patients with proven or indicated defects in either general (medium chain) or long chain acyl-CoA dehydrogenase have been reported. In recent years assays for the enzymatic diagnosis in cells, especially cultured skin fibroblasts, from such patients have been developed. The different methods are reviewed. The urinary excretion profile of organic acids from patients with fatty acyl-CoA dehydrogenase deficiencies are characterized by the presence of different compounds originating from the primary accumulated acyl-CoA ester(s). The most imp... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549971 Fri, 26 Jun 2009 06:28:51 +0100 2549971 Symptoms and signs in organic acidurias http://www.medworm.com/index.php?rid=2549972&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F80k2353170032k53%2F Abstract  Organic acidaemias can present with a wide variety of signs and symptoms. A survey of the clinical presentation of the organic acidurias shows that single symptoms are not characteristic or diagnostic. Clinical awareness coupled with appropriate laboratory investigation is required for the correct diagnosis to be reached. Content Type Journal ArticleCategory Clinical Aspects: Management And OutcomeDOI 10.1007/BF03047369Authors N. J. Brandt, University Department of Pediatrics, Rigshospitalet Section of Clinical Genetics Copenhagen Denmark Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 Journal Volume Volume 7 Journal Issue Volume 7, Supplement 1 / March, 1984 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549972 Fri, 26 Jun 2009 06:28:44 +0100 2549972 Prenatal diagnosis of the organic acidurias http://www.medworm.com/index.php?rid=2549973&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2130673ng2vv6t3%2F Abstract  Prenatal diagnosis for the genetic counselling of families at risk for having children with the life-threatening organic acidurias is advancing rapidly. The two major approaches to prenatal diagnosis are the assay for deficient activity of the enzymes in cultured amniocytes and the measurement of increased concentrations of the organic acids in the amniotic fluid. The latter, when done by stable isotope dilution analysis, is rapid, relatively inexpensive and very reliable. Content Type Journal ArticleCategory Clinical Aspects: Management And OutcomeDOI 10.1007/BF03047368Authors L. Sweetman, University of California Department of Pediatrics M-009 92093 San Diego, La Jolla CA USA Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549973 Fri, 26 Jun 2009 06:28:37 +0100 2549973 The management and long term outcome of organic acidaemias http://www.medworm.com/index.php?rid=2549974&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff36854352gq1l217%2F Abstract  We review the outcome of patients with maple syrup urine disease (14 classical patients and three variants), biotinidase deficiency (two patients) and non-cofactor-responsive variants of methylmalonic acidaemia (eight patients), propionic acidaemia (eight patients) and isolated 3-methylcrotonyl CoA carboxylase deficiency (three patients). Their survival, growth, intellectual development and other clinical problems are analysed. With the exception of isolated 3-methylcrotonyl CoA carboxylase deficiency the outcome of patients with disorders that are not cofactor responsive is disappointing. Twelve patients have died (five maple syrup urine disease, two methylmalonic acidaemia, five propionic acidaemia) and many of the survivors are developmentally retarded. The out... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549974 Fri, 26 Jun 2009 06:28:30 +0100 2549974 Mitochondrial oxidative phosphorylation and respiratory chain: Review http://www.medworm.com/index.php?rid=2549975&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx23u346xt6207650%2F Abstract  Basic events concerning oxidative phosphorylation, i.e. the synthesis of ATP at the expense of respired oxygen at the level of mitochondria are described. Our knowledge concerning the functioning of respiratory chain, its structure, organization and topology inside the inner membrane of mitochondria has considerably improved in recent years. A central question — how does the respiratory chain cooperate with ATP-synthetase, also embedded in the inner membrane, to bring about the oxidative phosphorylation of ADP to ATP — has been one of the most challenging and difficult problems in biochemical research. The chemiosmotic hypothesis proposed by the British biochemist Peter Mitchell appears best in describing the basic events of the recovery of the redox energy li... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549975 Fri, 26 Jun 2009 06:28:24 +0100 2549975 Animal models for dicarboxylic aciduria http://www.medworm.com/index.php?rid=2549976&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe411646112401m32%2F Abstract  Four compounds, 2[5(4-chlorophenyl)pentyl] oxirane-2-carboxylate (POCA), pent-4-enoate, hypoglycin and valproate, which are hypoglycaemic in fasted animals and form unusual acyl-CoA estersin vivo, inhibit mitochondrial β-oxidation by different mechanisms. POCA, hypoglycin and valproate are known to cause dicarboxylic aciduria. Saturated dicarboxylic acids are thought to be derived from long chain fatty acids by peroxisomal β-oxidation when mitochondrial β-oxidation is severely impaired. The use of these inhibitors provides animal models of dicarboxylic aciduria found in some inborn errors of metabolism. Content Type Journal ArticleCategory Dicarboxylic Acidurias And Acyl-CoA Dehydrogenase DeficienciesDOI 10.1007/BF03047375Authors H. S. A. Sherratt, Universit... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549976 Fri, 26 Jun 2009 06:28:17 +0100 2549976 Mitochondrial myopathies: Disorders of the respiratory chain and oxidative phosphorylation http://www.medworm.com/index.php?rid=2549977&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw65lu9pg06789433%2F Abstract  Mitochondrial myopathies are a clinical condition characterized by muscle weakness and fatigue in which the primary defect is localized at the level of the mitochondria. Microscopic examination shows accumulations of mitochondria at the fibre periphery (ragged red fibres) and in some cases mitochondrial paracrystalline inclusions. The spectrum of different mitochondrial defects so far described is reviewed and data from cases investigated in this laboratory are described. The first case was a 17-year-old boy with a multisystem disorder whose muscle mitochondria showed low respiratory activity with all substrates, which doubled in the presence of uncouples Further investigation showed that the mitochondrial ATPase activity was only 6 % of normal. The next cases wer... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549977 Fri, 26 Jun 2009 06:28:10 +0100 2549977 4-Hydroxybutyric aciduria: A new inborn error of metabolism. I. Clinical review http://www.medworm.com/index.php?rid=2549978&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdj88191622758m56%2F Content Type Journal ArticleCategory A New Disorder: 4-Hydroxybutyric AciduriaDOI 10.1007/BF03047381Authors D. Rating, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.F. Hanefeld, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.H. Siemes, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.J. Kneer, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.C. Jakobs, Academic Hospital of the Free University of Amsterdam Department of Pediatrics De Boelelaan 1117 1007 MB Amsterdam The NetherlandsM. Hermier, Hôpital Debro... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549978 Fri, 26 Jun 2009 06:28:03 +0100 2549978 Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis http://www.medworm.com/index.php?rid=2549979&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv917r5572rl80252%2F Abstract  The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review of the known causes of congenital lactic acidosis, are presented. Quantitative examination of the organic acids excreted by patients with proven enzyme deficiencies causing congenital lactic acidosis has demonstrated the characteristic patterns that are associated with specific disorders of this kind. After exclusion of uninherited, acquired and secondary metabolic causes of lactic acidosis, these quantitative patterns of organic acid excretion, toge... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549979 Fri, 26 Jun 2009 06:27:56 +0100 2549979 Lactic acidaemia http://www.medworm.com/index.php?rid=2549980&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcn14qj00754v0l58%2F Abstract  Congenital childhood lactic acidaemia is a poorly understood group of genetic diseases. The most common underlying inherited defect encountered in this group is deficiency of the pyruvate dehydrogenase complex. Of 23 cases we have diagnosed, 18 have a deficiency in the first component of the complex, the E1 decarboxylase, while the other five have multipleα-keto acid dehydrogenase deficiency due to a defect in lipoamide dehydrogenase. In addition to the lactic acidosis associated with pyruvate decarboxylase deficiency, ten of the cases showed evidence of facial dysmorphism consisting of a narrow head, wide nasal bridge and flared nostrils or gross microcephaly. Two further patients had agenesis of the corpus callosum. Isolated pyruvate carboxylase deficiency was f... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549980 Fri, 26 Jun 2009 06:27:49 +0100 2549980 Pyruvate carboxylase deficiency http://www.medworm.com/index.php?rid=2549981&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu2v54253hmh3086l%2F Abstract  The causes of congenital lactic acidaemia are outlined. Isolated pyruvate carboxylase deficiency is reviewed in detail with a report of a recent case and a discussion of the biochemical consequences. Other causes of defective pyruvate carboxylation are described, particularly the combined carboxylase defects. Content Type Journal ArticleCategory Disorders Of The Respiratory Chain And The Lactic AcidaemiasDOI 10.1007/BF03047379Authors K. Bartlett, University of Newcastle upon Tyne Department of Clinical Biochemistry and Metabolic Medicine NE1 7R U Newcastle upon Tyne UKH. K. Ghneim, University of Newcastle upon Tyne Department of Clinical Biochemistry and Metabolic Medicine NE1 7R U Newcastle upon Tyne UKJ. -H. Stirk, University of Newcastle upon Tyne Department o... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549981 Fri, 26 Jun 2009 06:27:41 +0100 2549981 4-Hydroxybutyric aciduria: A new inborn error of metabolism. II. Biochemical findings http://www.medworm.com/index.php?rid=2549982&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbx217183873k2442%2F Content Type Journal ArticleCategory A New Disorder: 4-Hydroxybutyric AciduriaDOI 10.1007/BF03047382Authors C. Jakobs, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.J. Kneer, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.D. Rating, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.F. Hanefeld, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.R.P. Divry, Hôpital Debrousse Laboratoire de Biochimie 29 rue Soeur Bouvier 69322 Lyon, Cedex 5 FranceM. Hermier, Hôpital Debrousse Laboratoire de Biochimie 29 rue Soe... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549982 Fri, 26 Jun 2009 06:27:34 +0100 2549982 4-Hydroxybutyric aciduria: A new inborn error of metabolism. III. Enzymology and inheritance http://www.medworm.com/index.php?rid=2549983&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft1451x8101808721%2F Content Type Journal ArticleCategory A New Disorder: 4-Hydroxybutyric AciduriaDOI 10.1007/BF03047383Authors K. M. Gibson, University of California Departments of Chemistry, Medicine and Pediatrics 92093 San Diego, La Jolla CA USAI. Jansen, University of California Departments of Chemistry, Medicine and Pediatrics 92093 San Diego, La Jolla CA USAL. Sweetman, University of California Departments of Chemistry, Medicine and Pediatrics 92093 San Diego, La Jolla CA USAW. L. Nyhan, University of California Departments of Chemistry, Medicine and Pediatrics 92093 San Diego, La Jolla CA USAD. Rating, Free University of Berlin Department of Pediatrics Kaiserin Auguste Victoria Haus, Heubnerweg 6 D-1000 Berlin 19 G.F.RC. Jakobs, Academic Hospital of the Free University of Amsterdam Department of P... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2549983 Fri, 26 Jun 2009 06:27:28 +0100 2549983 An unusual genetic variant in the MOCS1 gene leads to complete missplicing of an alternatively spliced exon in a patient with molybdenum cofactor deficiency http://www.medworm.com/index.php?rid=2500277&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0797861712t48658%2F We report an unusual mutation in the MOCS1 gene associated with a relatively mild clinical phenotype, in a patient who presented with normal uric acid (UA) levels in plasma. We also report a new MOCS1 mRNA splice variant in the 5′ region of the gene. MOCS1 genomic DNA and cDNA from peripheral blood leukocytes were sequenced. MOCS1 mRNA splice variants were amplified with fluorescently labelled primers and quantitated. A novel homozygous mutation MOCS1c.1165+6T > C in intron 9 resulting in miss-splicing of exon 9 was found. Multiple alternatively spliced MOCS1 transcripts have been previously reported. A new MOCS1 transcript in the 5′ – exon 1 region was identified in both patient and controls. This new transcript derived from the Larin variant and lacked exon 1 d. Conte... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2500277 Sat, 20 Jun 2009 06:06:13 +0100 2500277 Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK http://www.medworm.com/index.php?rid=2500278&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc441542623817731%2F Summary  Citrin deficiency is a disorder with two phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and adult-onset type II citrullinaemia (CTLN2). NICCD presents in the first few weeks of life with prolonged cholestasis and metabolic abnormalities including aminoacidaemia (notably citrulline, tyrosine, threonine, arginine and methionine) and galactosuria. Symptoms resolve within the first year of life, thus making a diagnosis difficult after this time. Although patients subsequently remain generally healthy, some may develop more severe symptoms of CTLN2, characterized by neurological changes, one or more decades later. To date more than 400 cases have been reported, almost all from East Asia (mainly Japan). Here we describe the first two c... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2500278 Thu, 11 Jun 2009 14:12:45 +0100 2500278 Four novel PDHA1 mutations in pyruvate dehydrogenase deficiency http://www.medworm.com/index.php?rid=2500279&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu065172g282371h2%2F This study adds four novel mutations to the around 90 reported mutations in PDHA1 (HGMD PDHA1 mutation database). The phenotypes of patients with PDH deficiency have been divided into three groups: a neonatal form with severe lactic acidosis, a form observed only in males and characterized by episodes of ataxia with relapses associated with hyperlactataemia, and an infantile form with hypotonia, lethargy, onset of seizures or dystonia, psychomotor retardation, in some cases Leigh-like lesions and mild to moderate hyperlactataemia. The four patients reported here all belong to the latter group, which is the largest. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1179-8Authors E. Ostergaard, Copenhagen University Hospital Rigshospitalet Department of Clinic... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2500279 Thu, 11 Jun 2009 14:12:44 +0100 2500279 Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: Assessing responsiveness in a model of statistical process control http://www.medworm.com/index.php?rid=2500280&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq5362g3101261048%2F Summary  Tetrahydrobiopterin (BH4) cofactor loading is a standard procedure to differentiate defects of BH4 metabolism from phenylalanine hydroxylase (PAH) deficiency. BH4 responsiveness also exists in PAH-deficient patients with high residual PAH activity. Unexpectedly, single cases with presumed nil residual PAH activity have been reported to be BH4 responsive, too. BH4 responsiveness has been defined either by a ≥30% reduction of blood Phe concentration after a single BH4 dose or by a decline greater than the individual circadian Phe level variation. Since both methods have methodological disadvantages, we present a model of statistical process control (SPC) to assess BH4 responsiveness. Phe levels in 17 adult PKU patients of three phenotypic groups off diet were compared ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2500280 Wed, 10 Jun 2009 11:28:47 +0100 2500280 Coenzyme Q10 is decreased in fibroblasts of patients with methylmalonic aciduria but not in mevalonic aciduria http://www.medworm.com/index.php?rid=2467111&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhq222m76r1w2j576%2F Summary  The content of coenzyme Q10 (CoQ10) was examined in skin fibroblasts of 10 patients with mevalonic aciduria (MVA) and of 22 patients with methylmalonic aciduria (MMA). Patients with these inborn errors of metabolism are thought to be at risk for CoQ10 depletion either by direct inhibition of the proximal pathway of CoQ10 synthesis (MVA) or indirectly by inhibition of mitochondrial energy metabolism (MMA). We demonstrated that CoQ10 concentrations were not significantly different from controls in MVA patients, suggesting that there may be upregulatory effects. On the other hand the CoQ10 content in fibroblasts of patients with MMA was significantly reduced. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10545-009-1150-8Authors D. Haas, University... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2467111 Sun, 07 Jun 2009 08:54:56 +0100 2467111 Black hip, fracture neck of femur and scoliosis: A case of ochronosis http://www.medworm.com/index.php?rid=2467112&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1688454727634x66%2F Conclusion: We report a case of scoliosis, fracture of the neck of the femur and ochronosis occurring together in a patient. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10545-009-1172-2Authors B. Zacharia, Government Medical College Calicut IndiaJ. Chundarathil, Government Medical College Thrissur IndiaV. Ramakrishnan, Government Medical College Thrissur IndiaR. M. Krishnankutty, Government Medical College Calicut IndiaR. Veluthedath, Government Medical College Calicut IndiaK. Puthezhath, Government Medical College Calicut IndiaI. Varughese, Government Medical College Calicut India Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease) Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2467112 Sun, 07 Jun 2009 08:54:55 +0100 2467112 Can we use statins to prevent stroke in Fabry disease? http://www.medworm.com/index.php?rid=2462350&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw2858g7r28ux8x4q%2F Summary  Fabry disease is a rare, X-linked lysosomal storage disease caused by an inborn deficiency of α-galactosidase A, which results in the progressive accumulation of globotriaosylceramide and other neutral glycolipids in a range of cells and tissues. In association with the renal and cardiac insufficiency, cerebrovascular complications can result in the death of the patients. Several mechanisms causing vascular damage that leads to the development of deep-white matter lesions have been described. Recent clinical trials strongly suggest that statins protect against stroke by neuroprotective properties or pleiotropic effects. Aim: To evaluate evidence and potential beneficial effects of statins in the vasculopathy of Fabry disease. Content Type Journal ArticleCategory... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2462350 Thu, 04 Jun 2009 10:00:54 +0100 2462350 Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency http://www.medworm.com/index.php?rid=2454355&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe120237346417714%2F Summary  In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134–147 ms; normal <118&nbsp... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2454355 Sat, 30 May 2009 08:06:53 +0100 2454355 Cognitive, behavioural and adaptive profiles of children with glutaric aciduria type I detected through newborn screening http://www.medworm.com/index.php?rid=2435736&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F850582637240l1n7%2F Conclusions: These findings highlight the importance of in-depth assessments of all aspects of neuropsychological function in patients with GA I and provide a basis for future neuropsychological assessment in similar groups of children. In spite of relatively preserved overall functioning, using a broad range of sensitive cognitive and motor measures facilitates the detection of subtle deficits, and allows for planning of early and adequate therapeutic interventions. Content Type Journal ArticleCategory Short ReportDOI 10.1007/s10545-009-1167-zAuthors M. H. Beauchamp, Australian Centre for Child Neuropsychological Studies Murdoch Children’s Research Institute Melbourne AustraliaA. Boneh, Royal Children’s Hospital Metabolic Service, Genetic Health Services Victoria, Murdoch Chil... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2435736 Sun, 24 May 2009 06:14:49 +0100 2435736 Chitotriosidase plasma activity in nephropathic cystinosis http://www.medworm.com/index.php?rid=2431404&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj81354702471k42g%2F Summary  Chitotriosidase is a fully active chitinase produced and secreted by activated phagocytes. Plasma chitotriosidase activity is a well-established marker of total disease burden in Gaucher disease that has proved useful in monitoring the response to both enzyme replacement and substrate reduction therapies in patients with Gaucher disease. Increased chitrotriosidase plasma activity has also been observed in several other lysosomal and non lysosomal disorders. Cystinosis, a rare multisystemic lysosomal storage disease, is characterized by the intralysosomal accumulation of free cystine in many cell types including phagocytes. We here report on plasma chitotriosidase activity in a child with nephropathic cystinosis. Increased plasma chitotriosidase activity (481nmol/h ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2431404 Wed, 20 May 2009 06:17:41 +0100 2431404 Neuroimaging findings in children with paediatric neurotransmitter diseases http://www.medworm.com/index.php?rid=2431403&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj35336468k0u2834%2F Summary  Paediatric neurotransmitter diseases consist of a group of inherited neurometabolic diseases in children, and include disorders related to γ-amino butyric acid (GABA) metabolism, monoamine biosynthesis, etc. The diagnosis of paediatric neurotransmitter diseases remain a great challenge for paediatricians and child neurologists. In addition to clinical manifestations and CSF neurotransmitter measurement, neuroimaging findings can also be very informative for the diagnosis and evaluation of the patients. For patients with monoamine biosynthesis disorders, the functional evaluation of dopaminergic transmission also plays an important role. Understanding of the possible neuroimaging changes in paediatric neurotransmitter diseases is therefore of great value for the in... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2431403 Wed, 20 May 2009 06:17:41 +0100 2431403 Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop http://www.medworm.com/index.php?rid=2426411&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0773w511v63765r4%2F Summary  Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2426411 Tue, 19 May 2009 06:01:55 +0100 2426411 Increasing physical function through physiatric intervention for children with paediatric neurotransmitter disorders http://www.medworm.com/index.php?rid=2421697&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa822242236r18221%2F We present a framework and rationale to the management of the functional consequences of the paediatric neurotransmitter diseases. Content Type Journal ArticleCategory SYMPOSIUM ON NEUROTRANSMITTER DISORDERSDOI 10.1007/s10545-009-1190-0Authors S. Evans, The George Washington University School of Medicine Department of Physiatry, Childrens National Medical Center 111 Michigan Avenue, NW Washington DC 20010 USAK. Forester, The George Washington University School of Medicine Department of Neurology, Childrens National Medical Center Washington DC USAJ. M. Pettiford, The George Washington University School of Medicine Department of Neurology, Childrens National Medical Center Washington DC USAO. Morozova, The George Washington University School of Medicine Department of Physiatry, Childr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=2421697 Sun, 17 May 2009 06:46:23 +0100 2421697