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. Thu, 09 Feb 2012 09:15:11 +0100 http://www.medworm.com/index.php?rid=5663258&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5t0271n1u15w454k%2F Abstract  NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3cyclohexanedione) is the mainstay of treatment in tyrosinemia type 1 (HT 1). The current recommendation is to divide the total daily dose of NTBC into two doses. We monitored the plasma NTBC concentrations in a series of seven patients who were changed from multiple divided doses to a single daily dose of NTBC. Two additional patients were started on a single daily dose of NTBC after the diagnosis of HT 1 was established. In three patients, NTBC kinetics were performed over 6 and 24 hours, respectively. The use of multiple divided doses or a single daily dose did not significantly affect plasma NTBC concentrations or the mean daily dose needed to attain therapeutic plasma NTBC concentrations. Moreover, kinetic studies ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663258 Fri, 03 Feb 2012 17:11:55 +0100 5663258 http://www.medworm.com/index.php?rid=5663259&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu448v277258k2447%2F Abstract  Prenylation consists of the addition of an isoprenoid group to a cysteine residue located near the carboxyl terminal of a protein. This enzymatic posttranslational modification is important for the maturation and processing of proteins. Both processes are necessary to mediate protein-protein and membrane-protein associations, in addition to regulating the localisation and function of proteins. The severe phenotype of animals deficient in enzymes involved in both prenylation and maturation highlights the significance of these processes. Moreover, alterations in the genes coding for isoprenylated proteins or enzymes that are involved in both prenylation and maturation processes have been found to be the basis of severe human diseases, such as cancer, neurodegenerati... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663259 Fri, 03 Feb 2012 17:11:53 +0100 5663259 http://www.medworm.com/index.php?rid=5663260&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd76872503jj38503%2F Abstract  When new technical possibilities arise in health care, often attunement is needed between different actors from the perspectives of research, health care providers, patients, ethics and policy. For cystic fibrosis (CF) such a process of attunement in the Netherlands started in a committee of the Health Council on neonatal screening in 2005. In the balancing of pros and cons according to Wilson and Jungner criteria, the advantages for the CF patient were considered clear, even though CF remains a severe health problem with treatment. Nevertheless, screening was not started then, mainly since the specificity of the tests available at that time was considered too low. Many healthy infants would have been referred for sweat testing and much uncertainty would arise in ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663260 Fri, 03 Feb 2012 07:20:33 +0100 5663260 http://www.medworm.com/index.php?rid=5663261&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frpw0x69172x7241x%2F Conclusions  The internet is an integral part of health care and an important source of information for newborn screening parents. Parents may benefit from recommendations of credible websites and discussions of internet information with health care providers. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s10545-011-9449-7Authors Jane M. DeLuca, University of Rochester, School of Nursing, 601 Elmwood Ave, Box SON, Rochester, NY 14642, USAMargaret H. Kearney, University of Rochester, School of Nursing, 601 Elmwood Ave, Box SON, Rochester, NY 14642, USASally A. Norton, University of Rochester, School of Nursing, 601 Elmwood Ave, Box SON, Rochester, NY 14642, USAGeorgianne L. Arnold, University of Pittsburgh, School of Medicine, 4401 Penn Ave,... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663261 Wed, 01 Feb 2012 17:13:54 +0100 5663261 http://www.medworm.com/index.php?rid=5663262&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7035743k370j65w4%2F Discussion  In contrast to our hypothesis, ADMA was lower and the L-arginine/ADMA ratio was higher in PKU patients. Therefore, in PKU patients, the regulating function of ADMA on NO synthesis is altered and may thus contribute to oxidative stress. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s10545-011-9448-8Authors M. Huemer, Department of Pediatrics, Landeskrankenhaus Bregenz, Carl Pedenz Str. 2, 6900 Bregenz, AustriaB. Simma, Department of Pediatrics, Landeskrankenhaus Feldkirch, Carinagasse 47, 6807 Feldkirch, AustriaD. Mayr, Department of Pediatrics, Landeskrankenhaus Bregenz, Carl Pedenz Str. 2, 6900 Bregenz, AustriaD. Möslinger, University Children’s Hospital, Währinger Gürtel 18-20, 1090 Vienna, AustriaA. Mühl, Centogene, Cam... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663262 Tue, 31 Jan 2012 07:04:28 +0100 5663262 http://www.medworm.com/index.php?rid=5663263&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx2x7557527u33574%2F Conclusion  Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10545-012-9451-8Authors Caroline Regnery, Friedrich-Baur Institute, Department of Neurology, Ludwig-Maximilians University Munich, Munich, GermanyCornelia Kornblum, Department of Neurology, University Hospital of Bonn, Bonn, GermanyFrank Hanisch, Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, GermanyStefan Vielhaber, Department of Neurology, University Hospital Magdeburg, Magdeburg, GermanyNicola Strigl-Pill, Friedrich-Baur Institute, Department of Neurology, Ludwig-Maximilians University Munich, Munich,... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5663263 Tue, 31 Jan 2012 07:04:27 +0100 5663263 http://www.medworm.com/index.php?rid=5642304&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5643776n06263176%2F Abstract  We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients (<5 years) at the mitral valve. At baseline, all patients had abnormal valves. The ECG showed no ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5642304 Wed, 25 Jan 2012 18:04:55 +0100 5642304 http://www.medworm.com/index.php?rid=5615419&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw03752v57637u238%2F Abstract  While it was thought that most of cerebral creatine is of peripheral origin, AGAT and GAMT are well expressed in CNS where brain cells synthesize creatine. While the creatine transporter SLC6A8 is expressed by microcapillary endothelial cells (MCEC) at blood-brain barrier (BBB), it is absent from their surrounding astrocytes. This raised the concept that BBB has a limited permeability for peripheral creatine, and that the brain supplies a part of its creatine by endogenous synthesis. This review brings together the latest data on creatine and guanidinoacetate transport through BBB and blood-CSF barrier (BCSFB) with the clinical evidence of AGAT-, GAMT- and SLC6A8-deficient patients, in order to delineate a clearer view on the roles of BBB and BCSFB in the transpor... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5615419 Wed, 18 Jan 2012 07:00:01 +0100 5615419 http://www.medworm.com/index.php?rid=5615420&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpt073502n7420n72%2F In conclusion, careful history taking and identification of suspicious symptoms in combination with a small number of rapidly available biochemical parameters are helpful to differentiate compensated metabolic condition and (impending) metabolic crisis and to decide when to start an emergency treatment. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s10545-011-9426-1Authors Tamaris Zwickler, Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, GermanyGisela Haege, Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, GermanyAlina Ridere... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5615420 Tue, 17 Jan 2012 07:16:07 +0100 5615420 http://www.medworm.com/index.php?rid=5615421&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F75302826x6538125%2F Abstract  The assessment of urinary α-aminoadipic semialdehyde (α-AASA) has become the diagnostic laboratory test for pyridoxine dependent seizures (PDS). α-AASA is in spontaneous equilibrium with its cyclic form Δ1-piperideine-6-carboxylate (P6C); a molecule with a heterocyclic ring structure. Ongoing diagnostic screening and monitoring revealed that in some individuals with milder ALDH7A1 variants, and patients co-treated with a lysine restricted diet, α-AASA was only modestly increased. This prompted us to investigate the diagnostic power and added value of the assessment of urinary P6C compared to α-AASA. Urine samples were diluted to a creatinine content of 0.1 mmol/L, followed by the addition of 0.01 nmol [2H9]pipecolic acid as internal standard (IS) and... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5615421 Tue, 17 Jan 2012 07:16:06 +0100 5615421 http://www.medworm.com/index.php?rid=5590752&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3833n74685113871%2F Abstract  Hyperinsulinaemic hypoglycaemia (HH) is due to the unregulated secretion of insulin from pancreatic β-cells. A rapid diagnosis and appropriate management of these patients is essential to prevent the potentially associated complications like epilepsy, cerebral palsy and neurological impairment. The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell KATP channel. At a histological level there are two major forms (diffuse and focal) each with a different genetic aetiology. The diffuse form is inherited in an autos... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590752 Mon, 09 Jan 2012 19:34:52 +0100 5590752 http://www.medworm.com/index.php?rid=5590753&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft0483537v2754641%2F Conclusion  The most significant finding is the high incidence of neonatal cardiomyopathy and hyperammonemia. Based on our experience, we propose a diagnostic flowchart applicable to critically ill neonates suspicious for MD. This tool will allow for the use of direct molecular genetic analyses without the need for muscle biopsies in neonates with Alpers, Barth, MILS and Pearson syndromes, SCO1, SCO2, TMEM70, ATP5E, SUCLG1 gene mutations and PDH complex deficiency. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s10545-011-9440-3Authors Tomas Honzik, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, 120 00 Prague 2, Czech Repub... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590753 Mon, 09 Jan 2012 19:34:51 +0100 5590753 http://www.medworm.com/index.php?rid=5590754&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa17616n3816r0m3m%2F Abstract  Previous histological and neuroimaging studies have documented structural abnormalities in the white matter of the brain in individuals with early-treated phenylketonuria (ETPKU). It remains unclear, however, the extent to which the function of the brain’s interconnections are impacted by this condition. Presently, we utilized functional magnetic resonance imaging (fMRI) to evaluate the synchronization of neural signals (i.e., functional connectivity) among brain regions comprising the default mode network (DMN) in a sample of 11 individuals with ETPKU and 11 age- and gender-matched neurologically intact controls. The DMN is a group of interconnected brain regions that are known to be generally more active during rest than during task performance. Data analysis ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590754 Mon, 09 Jan 2012 19:34:50 +0100 5590754 http://www.medworm.com/index.php?rid=5590756&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1hm7m61341m347w5%2F Abstract  The aim of newborn screening (NBS) programs is to detect a condition in a presymptomatic baby and provide management measures which could significantly improve the natural history of the disease. NBS programs for metabolic diseases were first introduced in North America and Europe and in the 1960s for phenylketonuria, expanded a few years later to include congenital hypothyroidism, and have been growing steadily in terms of number of conditions tested for and number of countries and births covered. Lysosomal storage diseases (LSDs) are a group of around 50 genetic conditions in which a defect in a lysosomal function occurs. LSDs are progressive conditions, being usually asymptomatic at birth, but with clinical features becoming apparent in childhood, with severe m... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590756 Mon, 09 Jan 2012 19:34:48 +0100 5590756 http://www.medworm.com/index.php?rid=5590755&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh86704073303024h%2F Conclusion  These preliminary findings suggest that children and adolescents with treated MPS have significantly poorer endothelial function when compared to healthy controls. Further investigation into the utility of endothelial function for risk stratification and the long term implications of reduced endothelial function in MPS is warranted. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s10545-011-9438-xAuthors Aaron S. Kelly, Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Medical School, 420 Delaware St. S.E., MMC 715, Minneapolis, MN 55455, USAAndrea M. Metzig, Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Medical School, 420 Delaw... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590755 Mon, 09 Jan 2012 19:34:48 +0100 5590755 http://www.medworm.com/index.php?rid=5590760&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F720kv16371822210%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10545-011-9442-1Authors Jennifer Cialone, University of Rochester, Rochester, NY, USAHeather Adams, University of Rochester, Rochester, NY, USAErika F. Augustine, University of Rochester, Rochester, NY, USAFrederick J. Marshall, University of Rochester, Rochester, NY, USAJennifer M. Kwon, University of Rochester, Rochester, NY, USANicole Newhouse, University of Rochester, Rochester, NY, USAAmy Vierhile, University of Rochester, Rochester, NY, USAErika Levy, University of Rochester, Rochester, NY, USALeon S. Dure, University of Rochester, Rochester, NY, USAKatherine R. Rose, University of Rochester, Rochester, NY, USADenia Ramirez-Montealegre, University of Rochester, Rochester, NY, USAElisabeth A. de Blieck, University o... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590760 Mon, 09 Jan 2012 19:34:47 +0100 5590760 http://www.medworm.com/index.php?rid=5590759&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy54u028444p18613%2F Content Type Journal ArticleCategory Letter to the EditorsPages 1-2DOI 10.1007/s10545-011-9402-9Authors Mara Doimo, Clinical Genetics Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, ItalyEva Trevisson, Clinical Genetics Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, ItalyGeppo Sartori, Department of Biochemistry, University of Padova, Viale G. Colombo, 3 - 35121 Padova, ItalyAlberto Burlina, Metabolic Disorders Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, ItalyLeonardo Salviati, Clinical Genetics Unit, Department of Pediatrics, University of Padova, Via Giustiniani 3, 35128 Padova, Italy Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590759 Mon, 09 Jan 2012 19:34:47 +0100 5590759 http://www.medworm.com/index.php?rid=5590758&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03l2g14213l710n0%2F Abstract  Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590758 Mon, 09 Jan 2012 19:34:47 +0100 5590758 http://www.medworm.com/index.php?rid=5590757&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg53920258uk1782p%2F Abstract  Riboflavin and ubiquinone (Coenzyme Q10, CoQ10) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B2)-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been detected in Brown-Vialetto-Van Laere and Fazio-Londe syndromes (C20orf54), and haploinsufficiency of GPR172B has been proposed in one patient to cause persistent riboflavin deficiency. Mutations in the electron tranferring fravoprotein genes (ETFA/ETFB) and its dehydrogenase (ETFDH) are causative for multiple acyl-CoA dehydrogenase deficiency. Mutations in ACAD9, encoding the acyl-CoA dehydrogenase 9 protein were recently reported in mitochondrial disease with r... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590757 Mon, 09 Jan 2012 19:34:47 +0100 5590757 http://www.medworm.com/index.php?rid=5590761&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx492722481130883%2F Abstract  A patient with suspected glutaric aciduria type 1 (GA-1) was detected by newborn screening. GA-1 is known as an autosomal recessively inherited disease due to defects in the gene coding for glutaryl-CoA dehydrogenase (GCDH), a mitochondrial enzyme involved in the catabolism of the amino acids hydroxylysine, lysine and tryptophan. DNA and cDNA sequencing revealed a 18 bp deletion (c.553_570del18) resulting in deletion of six amino acids (p.Gly185_Ser190del) in one allele and no sequence changes in the other allele. Confirmatory biochemical analysis of blood, urine and cultured fibroblasts from the proband were consistent with a mild biochemical GA-1 phenotype. Recombinant expression of the mutant variant in E. coli showed that the GCDH-(p.Gly185_Ser190del) prot... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5590761 Mon, 09 Jan 2012 19:34:46 +0100 5590761 http://www.medworm.com/index.php?rid=5541529&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu73518086266125r%2F Abstract  The traditional focus of newborn screening (NBS) is testing infants for medical conditions like phenylketonuria (PKU) that may cause significant morbidity or mortality unless treatment is initiated early. Although the Wilson and Jungner criteria were not designed specifically for NBS, the public health screening criteria have been used, with some modifications, to justify what conditions are included in a universal NBS panel. These criteria are being challenged by platform technologies like tandem mass spectrometry (MS/MS) that allow for the identification of numerous conditions on a single sample because they identify many conditions and variants simultaneously, some of which meet and others which fail to meet the criteria. In this manuscript, I evaluate three ly... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5541529 Wed, 21 Dec 2011 20:06:50 +0100 5541529 http://www.medworm.com/index.php?rid=5541530&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fth6024145g48021j%2F Discussion  Our results suggest the interference of VPA with the activity of 3MCC through a potential cumulative effect: direct inhibition of the enzyme activity by the drug metabolite valproyl-CoA and the inhibition of biotinidase by valproate and/or its metabolites. These interactions may be associated with the skin rash and hair loss which are side effects often reported in VPA-treated patients. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s10545-011-9423-4Authors Paula B. M. Luís, Research Institute for Medicines and Pharmaceutical Sciences, iMed.UL, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, PortugalJos P. Ruiter, Department of Clinical Chemistry and Pediatrics, Academic Medical Center, Amsterdam, Meibergdreef 9, 110... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5541530 Wed, 21 Dec 2011 20:06:49 +0100 5541530 http://www.medworm.com/index.php?rid=5541531&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2660223n12257310%2F Abstract  X−linked adrenoleukodystrophy is a rare inherited demyelinating disorder characterized by an abnormal accumulation of very long chain fatty acids, mainly hexacosanoic acid (26:0), due to a mutation of the gene encoding for a peroxisomal membrane protein. The only available, and partially effective, therapeutic treatment consists of dietary intake of a 4:1 mixture of triolein and trierucin, called Lorenzo’s oil (LO), targeted to inhibit the elongation of docosanoic acid (22:0) to 26:0. In this study we tested whether, besides inhibiting elongation, an enhancement of peroxisomal beta oxidation induced by conjugated linoleic acid (CLA), will improve somatosensory evoked potentials and modify inflammatory markers in adrenoleukodystrophy females carriers. We enroll... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5541531 Wed, 21 Dec 2011 20:06:48 +0100 5541531 http://www.medworm.com/index.php?rid=5541532&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6510681x164p38h7%2F This study provides additional evidence for a synergistic effect between ERT and pharmacological chaperone therapy and supports the idea that the efficacy of combination protocols may be superior to ERT alone. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s10545-011-9424-3Authors Caterina Porto, Department of Pediatrics, Federico II University, Via S. Pansini 5, 80131 Naples, ItalyAntonio Pisani, Department of Nephrology, Federico II University, Naples, ItalyMargherita Rosa, Department of Pediatrics, Federico II University, Via S. Pansini 5, 80131 Naples, ItalyEmma Acampora, Department of Pediatrics, Federico II University, Via S. Pansini 5, 80131 Naples, ItalyValeria Avolio, Department of Pediatrics, Federico II University, Via S. Pansini 5, 80131 Naple... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5541532 Tue, 20 Dec 2011 16:44:13 +0100 5541532 http://www.medworm.com/index.php?rid=5510527&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F56666g816j58571v%2F Abstract  Δ1-Pyrroline-5-carboxylate synthetase (P5CS) catalyzes the first two steps of ornithine/proline biosynthesis. P5CS deficiency has been reported in three families, with patients presenting with cutis/joint laxity, cataracts, and neurodevelopmental delay. Only one family exhibited metabolic changes consistent with P5CS deficiency (low proline/ornithine/citrulline/arginine; fasting hyperammonemia). Here we report a new P5CS-deficient patient presenting the complete clinical/metabolic phenotype and carrying p.G93R and p.T299I substitutions in the γ-glutamyl kinase (γGK) component of P5CS. The effects of these substitutions are (1) tested in mutagenesis/functional studies with E.coli γGK, (2) rationalized by structural modelling, and (3) reflected in decreased P5CS ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5510527 Wed, 14 Dec 2011 16:41:49 +0100 5510527 http://www.medworm.com/index.php?rid=5510528&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7155725162p3734%2F Abstract  The 1991 introduction of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) as a treatment for hereditary tyrosinemia type 1 (HT-1), a disorder of tyrosine catabolism, has radically modified the natural history of this disorder. Despite the dramatic improvements in survival, outcomes and quality of life seen with NTBC treatment, HT-1 remains a chronic disorder with several long-term complications, including, a persistent (albeit low) risk of hepatocellular carcinoma and suboptimal neuropsychological outcomes. There remain unsolved key-questions concerning the long-term outcomes of patients with HT-1, which closely depend on the quality of follow-up in these patients. In the absence of published guidelines, we investigated the follow-up methods used ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5510528 Tue, 13 Dec 2011 17:06:12 +0100 5510528 http://www.medworm.com/index.php?rid=5510529&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F17q3606637506144%2F Content Type Journal ArticleCategory Letter to the EditorsPages 1-1DOI 10.1007/s10545-011-9431-4Authors Chitra Prasad, London Health Sciences Centre, London, Ontario, CanadaA. E. Cairney, London Health Sciences Centre, London, Ontario, CanadaD. S. Rosenblatt, Department of Human Genetics, McGill University, Quebec, CanadaC. A. Rupar, London Health Sciences Centre, London, Ontario, Canada 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=5510529 Tue, 13 Dec 2011 17:06:11 +0100 5510529 http://www.medworm.com/index.php?rid=5510530&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg1373q2j38h61011%2F Abstract  Urea cycle disorders (UCDs) are one of the most frequently inherited metabolic diseases in Japan, with an estimated prevalence of 1 per 50,000 live births. Here, we investigated the clinical manifestations, treatment, and prognosis of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009. These included 77 cases of neonatal-onset UCDs and 91 cases of late-onset UCDs. The most common UCD was ornithine transcarbamylase deficiency (OTCD), which accounted for 116 out of 177 patients. This result is similar to a previous study performed between 1978 and 1995 in Japan: OTCD accounted for about two-thirds of the total number of UCD cases. We studied the relationship between prognosis and the peak blood ammonia level at the onset in 151 UCD... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5510530 Tue, 13 Dec 2011 17:06:10 +0100 5510530 http://www.medworm.com/index.php?rid=5510531&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F082p314u2r8xwm82%2F Abstract  Cardiovascular survival in a cohort of 33 male Fabry patients followed for a median of 7.3 years at a single centre was most strongly associated in a Cox proportional hazard regression model with age and elevated arterial stiffness at baseline. Seven patients died of cardiovascular causes. The presence of cardiomyopathy and renal involvement (either clinical nephropathy or CKD stage >1) were also negatively associated with survival when analysed as single factors. In this small study, presence of hypertension and hypercholesterolemia at baseline did not significantly predict cardiovascular death. The significant effect of elevated arterial stiffness, especially in a small cohort, argues for its clinical utility in individual patient risk assessment and for... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5510531 Tue, 13 Dec 2011 17:06:09 +0100 5510531 http://www.medworm.com/index.php?rid=5510532&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F717422vwqp115w12%2F Abstract  Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood. Symptoms typically present at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. Studies on sex differences in JNCL have yielded mixed results, but parent anecdotes suggest that females experience a more precipitous disease course. Therefore, we sought to determine if sex-based differences exist in JNCL. We used data from the Unified Batten Disease Rating Scale (UBDRS), the Batten Disease Support and Research Association (BDSRA) database, and the PedsQL quality of life (QoL) survey to evaluate sex-based differences in functional independence and time fr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5510532 Tue, 13 Dec 2011 17:06:08 +0100 5510532 http://www.medworm.com/index.php?rid=5481614&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft862030210100x3r%2F Conclusions  Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s10545-011-9422-5Authors Radan Bruha, First Faculty of Medicine, 4th Department of Internal Medicine, Charles University in Prague, Prague, Czech RepublicLibor Vitek, First Faculty of Medicine, 4th Department of Internal Medicine, Charles University in Prague, Prague, Czech RepublicZdenek Marecek, Department of Internal Medicine, Central Military Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech RepublicLenka Pospisilova, 1st Faculty of Medicine, Pediatric Depar... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5481614 Fri, 02 Dec 2011 18:08:45 +0100 5481614 http://www.medworm.com/index.php?rid=5481613&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftg14l753111556v1%2F Content Type Journal ArticleCategory EditorialPages 1-1DOI 10.1007/s10545-011-9420-7Authors Jörn Oliver Sass, Labor für Klinische Biochemie & Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstr. 1, 79106 Freiburg, Germany 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=5481613 Fri, 02 Dec 2011 18:08:45 +0100 5481613 http://www.medworm.com/index.php?rid=5472755&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0038x5k62ql1041%2F In this report, we propose a completely novel concept regarding the pathogenesis of FAS. Based on our observation that transferrin isoelectric focusing (TIEF) – the most widely used screening tool for congenital disorders of glycosylation (CDG) – was transiently abnormal in a newborn with FAS and a confirmed maternal history of gestational alcohol abuse, we came to believe that FAS exemplifies a congenital disorder of glycosylation secondary to alcohol-inflicted disruption of (N-linked) protein glycosylation. Various pieces of evidence were found in the literature to substantiate this hypothesis. This observation implies, among others, that one might need to consider the possibility of maternal alcohol consumption in newborns with transient glycosylation abnormalities. We also p... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5472755 Thu, 01 Dec 2011 19:31:46 +0100 5472755 http://www.medworm.com/index.php?rid=5472756&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn86041u748376867%2F Conclusion  Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications. Content Type Journal ArticleCategory Branched-Chain Amino AcidsPages 1-9DOI 10.1007/s10545-011-9419-0Authors S. C. Grünert, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Freiburg, GermanyS. Müllerleile, Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstr. 1, 79106 Freiburg, GermanyL. de Silva, Labor für Klinische Biochemie und Stoffwechsel, Zentr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5472756 Thu, 01 Dec 2011 19:31:45 +0100 5472756 http://www.medworm.com/index.php?rid=5472757&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy3025757h1334501%2F Abstract  The HSD17B10 gene is located on chromosome Xp11.2 and codes for a multifunctional protein called 17β-hydroxysteroid dehydrogenase type 10 (HSD10). This protein catalyzes the 2-methyl-3-hydroxybutyryl-CoA dehydrogenation (MHBD) reaction in isoleucine metabolism and is an essential component of mitochondrial RNase P required for the processing of mtDNA transcripts. HSD10 is required for normal mitochondrial maintenance, and complete loss of HSD10 is incompatible with life. Mutations in the HSD17B10 gene have been reported in 19 families. The classical infantile form of what is best named HSD10 disease is characterized by a period of more or less normal development in the first 6-18 months of life. Some patients showed transient metabolic derangement in the neonatal ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5472757 Wed, 30 Nov 2011 04:36:23 +0100 5472757 http://www.medworm.com/index.php?rid=5472758&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp41j3j815807775q%2F Conclusions  The CSP represents the largest cross-sectional study of MPS VI to date. This first report provides information on the design and implementation of the program and population statistics for several clinical variables in patients with MPS VI. Data collected over 5 years suggest that ERT provides clinical benefit and is well-tolerated with no new safety concerns. Content Type Journal ArticleCategory Original ArticlePages 1-12DOI 10.1007/s10545-011-9410-9Authors Christian J. Hendriksz, Birmingham Children’s Hospital, Birmingham, UKRoberto Giugliani, Department of Genetics/UFRGS, Medical Genetics Service/HCPA and INAGEMP, Porto Alegre, BrazilPaul Harmatz, Children’s Hospital & Research Center Oakland, Oakland, CA, USAChristina Lampe, Villa Metabolica... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5472758 Wed, 30 Nov 2011 04:36:22 +0100 5472758 http://www.medworm.com/index.php?rid=5452986&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl0872xvw86138872%2F Abstract  Phenylketonuria represents the most prevalent inborn error of amino acid metabolism. In early diagnosed patients adequate and continued dietary treatment results in a good neurologic outcome. Natural protein and phenylalanine-restricted diet, even if rich in fruits and vegetables, represents a serious risk for nutritional deficiencies, albeit universally accepted. In the last few years, a growing number of reports have been describing oxidative stress as a concern in phenylketonuric patients. The diet itself includes good sources of dietary antioxidants (phytochemicals, some vitamins and minerals) but also a risk factor for some deficiencies (selenium, zinc, ubiquinone-10 and L-carnitine). Additionally, the extreme stringency of the diet may impose a reduced synth... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5452986 Thu, 24 Nov 2011 17:45:08 +0100 5452986 http://www.medworm.com/index.php?rid=5452987&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu45411h331837702%2F Abstract  Derivatives of folic acid are involved in transfer of one-carbon units in cellular metabolism, playing a role in synthesis of purines and thymidylate and in the remethylation of homocysteine to form methionine. Five inborn errors affecting folate transport and metabolism have been well studied: hereditary folate malabsorption, caused by mutations in the gene encoding the proton-coupled folate transporter (SLC46A1); glutamate formiminotransferase deficiency, caused by mutations in the FTCD gene; methylenetetrahydrofolate reductase deficiency, caused by mutations in the MTHFR gene; and functional methionine synthase deficiency, either as the result of mutations affecting methionine synthase itself (cblG, caused by mutations in the MTR gene) or affecting the accessory ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5452987 Tue, 22 Nov 2011 17:57:24 +0100 5452987 http://www.medworm.com/index.php?rid=5426868&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv324m87gl3805v02%2F Abstract  Born at 27 weeks gestation, a child of consanguineous parents of Pakistani origin required prolonged parenteral nutrition. She developed jaundice, with extensive fibrosis and architectural distortion at liver biopsy; jaundice resolved with supportive care. Serum γ-glutamyl transpeptidase values were within normal ranges. The bile acids in her plasma and urine were >85% unconjugated (non-amidated). Two genes encoding bile-acid amidation enzymes were sequenced. No mutations were found in BAAT, encoding bile acid-CoA : aminoacid N-acyl transferase. The patient was homozygous for the missense mutation c.1012C > T in SLC27A5, predicted to alter a highly conserved amino-acid residue (p.H338Y) in bile acid-CoA ligase (BACL). She also was homozygous for the... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5426868 Wed, 16 Nov 2011 16:47:28 +0100 5426868 http://www.medworm.com/index.php?rid=5426869&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr632m6122u507770%2F We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10545-011-9413-6Authors Emma Glamuzina, Department of Metabolic Medicine, Great Ormond Street Hospital for Children, London, UKRuth Brown, Department of Biochemistry, University of Oxford, Oxford, UKKieran Hogarth, Department of Radiology, Great Ormond Street Hospital for Children, London, UKDawn Saunders, Department of Radiology, Great Ormond Street Hospital for Children, London, UKIsabelle Russell-Eggitt, Department of Ophthalmology, Ulverscroft Vision R... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5426869 Tue, 15 Nov 2011 16:57:26 +0100 5426869 http://www.medworm.com/index.php?rid=5415360&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F70802808qlr6758j%2F Content Type Journal ArticleCategory Letter to the EditorsPages 1-1DOI 10.1007/s10545-011-9414-5Authors M. Albersen, Department of Metabolic Diseases, University Medical Center (UMC) Utrecht, Utrecht, The NetherlandsM. van der Ham, Department of Metabolic Diseases, University Medical Center (UMC) Utrecht, Utrecht, The NetherlandsN. M. Verhoeven-Duif, Department of Metabolic Diseases, University Medical Center (UMC) Utrecht, Utrecht, The NetherlandsF. Groenendaal, Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Center (UMC) Utrecht, Utrecht, The NetherlandsM. G. M. de Sain-van der Velden, Department of Metabolic Diseases, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5415360 Mon, 14 Nov 2011 16:54:51 +0100 5415360 http://www.medworm.com/index.php?rid=5415361&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0114831x1441473n%2F Conclusion  The results suggest effects on BA and on BMD, in both children and adolescent groups. The bone development is expressed differently in children and adolescents. The non-adherence to the diet verified in both groups and the consequent imbalance in the nutrients intake involved in bone metabolism suggest that these factors influence the failure to thrive in children and reduced bone mineralization in adolescents. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s10545-011-9412-7Authors A. B. Mendes, Mestrado em Atenção Integrada à Saúde da Criança e do Adolescente, Faculdade de Medicina da Universidade Federal Fluminense, Santos Moreira Street, 89 / 7 Santa Rosa, 24241080 Niterói, Rio de Janeiro, BrazilF. F. Martins, Mestrado ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5415361 Thu, 10 Nov 2011 16:52:57 +0100 5415361 http://www.medworm.com/index.php?rid=5415362&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F70167m6337n75934%2F This study shows that proteolytic techniques can reveal conformational abnormalities even for CBS mutants that have activity and/or a degree of assembly similar to the wild-type enzyme. We present here a methodological strategy that may be used in cell lysates to evaluate properties of proteins that tend to misfold and aggregate and that may be important for conformational studies of disease-causing mutations in the field of inborn errors of metabolism. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10545-011-9407-4Authors Aleš Hnízda, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, 128 08 Prague 2, Czech RepublicVojtěch Jurga, Department of ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5415362 Wed, 09 Nov 2011 07:02:43 +0100 5415362 http://www.medworm.com/index.php?rid=5415363&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe58n25qp627r25jq%2F Conclusions  A high number of patients performed below normal in the assessment of development, motor function and speech. We propose intellectual impairment as long-term complication in HT type I with elevated plasma tyrosine under NTBC treatment as observed in other hypertyrosinemias. These findings remain to be reproduced in greater patient numbers. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s10545-011-9394-5Authors Eva Thimm, Department of General Pediatrics, Medical Faculty, University Dusseldorf, Moorenstrasse 5, 40225 Düsseldorf, GermanyRenate Richter-Werkle, Department of General Pediatrics, Medical Faculty, University Dusseldorf, Moorenstrasse 5, 40225 Düsseldorf, GermanyGudrun Kamp, Department of General Pediatrics, Medical ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5415363 Wed, 09 Nov 2011 07:02:42 +0100 5415363 http://www.medworm.com/index.php?rid=5371930&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6517140513818126%2F Abstract  Fabry disease is an X-linked disorder caused by a deficiency of α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms – agalsidase alfa and agalsidase beta – have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain dif... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5371930 Sat, 29 Oct 2011 05:49:54 +0100 5371930 http://www.medworm.com/index.php?rid=5371931&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn852352754255669%2F Abstract  Unlike replacement therapy by infusion of exogenous recombinant lysosomal enzymes, pharmacological chaperones aim at a gain of function of endogenous gene products. Deficits resulting from missense mutations may become treatable by small, competitive inhibitors binding to the catalytical site and thus correcting the erroneous conformation of mutant enzymes. This may prevent their premature degradation and normalize intracellular trafficking as well as biological half-life. A major limitation currently arises from the huge number of individual missense mutations and the lack of knowledge on the structural requirements for specific interaction with mutant protein domains. Our previous work on mutations of the β-galactosidase (β-gal) gene, causing GM1 gangliosidosi... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5371931 Fri, 28 Oct 2011 06:05:48 +0100 5371931 http://www.medworm.com/index.php?rid=5371932&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk8jj315010l861n1%2F This study adds a considerable amount of new molecular data to the studies of this disease. Content Type Journal ArticleCategory Original ArticlePages 1-13DOI 10.1007/s10545-011-9399-0Authors J. P. Kraus, Department of Pediatrics and the Colorado Intellectual and Developmental Disabilities Research Center (IDDRC), University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USAE. Spector, Department of Pediatrics and the Colorado Intellectual and Developmental Disabilities Research Center (IDDRC), University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USAS. Venezia, Department of Pediatrics and the Colorado Intellectual and Developmental Disabilities Research Center (IDDRC), University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, US... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5371932 Thu, 27 Oct 2011 15:46:25 +0100 5371932 http://www.medworm.com/index.php?rid=5353601&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd795640tn82m0v53%2F We report here the first autopsy case of a child with a genetically confirmed diagnosis of EE, and compare the histological, histochemical and immunohistochemical findings with those of the constitutive Ethe1 −/− mice. In addition to COX depleted cells, widespread endothelial lesions of arterioles and capillaries of the brain and gastrointestinal tract were the pathologic hallmarks in both organisms. Our findings of diffuse vascular damage of target critical organs are in keeping with the hypothesis that the pathologic effects of ETHE1 deficiency may stem from high levels of circulating hydrogen sulphide rather than the inability of specific organs to detoxify its endogenous production. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s10545-011-9408-... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5353601 Fri, 21 Oct 2011 15:51:20 +0100 5353601 http://www.medworm.com/index.php?rid=5341961&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl143815056182637%2F We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s10545-011-9406-5Authors Jonathan J. Rios, Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USASavitha Shastry, Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USAJuan Jasso, Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USANatalie Hauser, Eugene McDermott Center for Human Growth and Development, University of Texas So... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5341961 Wed, 19 Oct 2011 05:54:44 +0100 5341961 http://www.medworm.com/index.php?rid=5341962&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkw127g4617271720%2F This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months −12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5341962 Wed, 19 Oct 2011 05:54:43 +0100 5341962 http://www.medworm.com/index.php?rid=5341963&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3611533714g15p28%2F Abstract  Glutaric acidemia type I (GA1) is associated with elevated glutarylcarnitine (C5DC), typically measured as its butylester by acylcarnitine profile analysis using tandem mass spectrometry (MS/MS) and the precursor-product ion pair of m/z 388-85. This method neither distinguishes between C5DC and its isomer 3-hydroxydecanoylcarnitine (C10-OH) nor reliably detects the low-excretor variant of GA1, leading to both false-positive and false-negative results when testing for GA1. To overcome these limitations, we developed an LC-MS/MS method that discriminates C5DC from C10-OH by the use of precursor-product ion pairs specific for butylated C5DC (m/z 388-115) and underivatized C10-OH (m/z 332-85). The C5DC method was validated over the linearity range of 0.025–20 μM... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5341963 Tue, 18 Oct 2011 05:58:58 +0100 5341963 http://www.medworm.com/index.php?rid=5328956&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7hx72l138217417%2F Conclusion  Prediction of the outcome of GE may be facilitated by recognizing selected clinical parameters and early neuroimaging findings. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10545-011-9398-1Authors Julia B. Hennermann, Department of Pediatrics, Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, GermanyJeanne-Marie Berger, Department of Pediatrics, Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, GermanyUlrike Grieben, Department of Neuropediatrics, Charité Universitätsmedizin, Berlin, GermanyGunter Scharer, Department of Pediatrics, University of Colorado, Aurora, CO, USAJohan L. K. Van Hove, Department of Pediatrics, University of Colorado, Aurora, CO, USA Journal Journal of Inherite... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5328956 Fri, 14 Oct 2011 15:42:56 +0100 5328956 http://www.medworm.com/index.php?rid=5328955&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frk66478441327th5%2F Abstract  Mucopolysaccharidoses (MPSs) are lysosomal storage diseases (LSDs) caused by defects in lysosomal enzymes involved in the catabolism of glycosaminoglycans. The pathogenesis of these disorders is still not completely known, although inflammation and oxidative stress appear to be common mechanisms, as in all LSDs. Recently, it was hypothesized that endoplasmic reticulum (ER) stress followed by an unfolded protein response (UPR) could be another common pathogenetic mechanism in LSDs. The aim of the present study was to verify if the UPR was elicited in the mucopolysaccharidoses and if the mechanism was MPS type- and mutation-dependent. To this end, we analyzed the UPR in vitro, in fibroblasts from patients with different types of mucopolysaccharidoses (MPS I, II, III... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5328955 Fri, 14 Oct 2011 15:42:56 +0100 5328955 http://www.medworm.com/index.php?rid=5328957&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F97r3u735h97801m7%2F Abstract  Hearing loss has been recognized as an important cause of morbidity in infants with Pompe disease, a metabolic disorder caused by deficiency of acid α-glucosidase. It is unknown whether hearing is also affected in adult Pompe patients. We have studied the prevalence, severity, and type of hearing loss in 58 adult patients using tympanometry and pure-tone audiometry. Compared to normative data (International Organisation for Standardisation standard 7029), 72% of patients had impaired hearing thresholds at one or more frequencies in at least one ear. All measured frequencies were equally affected. All patients had a sensorineural type of hearing loss, pointing to cochlear or retrocochlear pathology. Categorised according to the standards of the World Health Organi... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5328957 Fri, 14 Oct 2011 15:42:55 +0100 5328957 http://www.medworm.com/index.php?rid=5328958&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx07g8h13575k343w%2F Abstract  Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder affecting fumarylacetoacetate hydrolase (FAH), the last enzyme in the tyrosine catabolism pathway. The liver mosaicism observed in HT1 patients is due to the reversion to the wild type of one allele of the original point mutation in fah. It is generally accepted that these reversions are true back mutations; however, the mechanism is still unresolved. Previous reports excluded intragenic recombination, mitotic recombination, or homologous recombination with a pseudogene as possible mechanisms of mutation reversion in HT1. Sequence analysis did not reveal DNA motifs, tandem repeats or other sequence peculiarities that may be involved in mutation reversion. We propose the hypothesis that a point m... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5328958 Fri, 14 Oct 2011 15:42:50 +0100 5328958 http://www.medworm.com/index.php?rid=5309400&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F557191652122n412%2F We examined the efficacy of 2-year enzyme replacement therapy (ERT) using recombinant human α-glucosidase (GAA; Myozyme®) in five long-term ventilator-dependent adults and aged patients with advanced, late-onset glycogen storage disease type II (GSDII, also known as Pompe disease). Although all patients had advanced respiratory failure and were ventilator-dependent for more than 6 years, four showed obvious improvements in muscle strength, pulmonary function, and activities of daily living after ERT. Improvement in each parameter was more prominent in the first year than in the second year. Values in the second year were still significantly better than those at study entry and indicate stabilization in the clinical status of all patients. These results suggest that ERT continu... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5309400 Sat, 08 Oct 2011 05:52:46 +0100 5309400 http://www.medworm.com/index.php?rid=5300890&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbhrx101534275038%2F Abstract  The functional significance of missense mutations in genes encoding acid glycosidases of lysosomal storage disorders (LSDs) is not always clear. Here we describe a method of investigating functional properties of variant enzymes in vitro using a human embryonic kidney epithelial cell line. Site-directed mutagenesis was performed on the parental plasmids containing cDNA encoding for alpha-galactosidase A (α-Gal A) and acid maltase (α-Glu) to prepare plasmids encoding relevant point mutations. Mutant plasmids were transfected into HEK 293 T cells, and transient over-expression of variant enzymes was measured after 3 days. We have illustrated the method by examining enzymatic activities of four unknown α-Gal A and one α-Glu variants identified in our patient... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5300890 Wed, 05 Oct 2011 05:49:11 +0100 5300890 http://www.medworm.com/index.php?rid=5279918&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb118782132153530%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10545-011-9397-2Authors Manuel Schiff, Reference Center for Metabolic Disease, Robert Debré University Hospital, APHP, Paris, FranceJean-François Benoist, Reference Center for Metabolic Disease, Robert Debré University Hospital, APHP, Paris, FranceBogdana Tilea, Pediatric Radiology, Robert Debré University Hospital, APHP, Paris, FranceNicolas Royer, Reference Center for Metabolic Disease, Robert Debré University Hospital, APHP, Paris, FranceStéphane Giraudier, Haematology Laboratory, Henri Mondor University Hospital, AP-HP, Créteil, FranceHélène Ogier de Baulny, Pediatric Neurology & Metabolic disease, Robert Debré University Hospital, APHP, Paris, France Journal Journal of Inherited Metabolic DiseaseOnl... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5279918 Tue, 27 Sep 2011 05:52:38 +0100 5279918 http://www.medworm.com/index.php?rid=5279917&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7173v38650131t7%2F We present a review of our experience and pregnancy outcome in patients with GSD III managed by our centre. Between 1997 and 2010 there were 15 pregnancies in seven women with GSD III. Four women had GSD IIIb (nine pregnancies) and three GSD IIIa (six pregnancies). There was a successful outcome in all 15 pregnancies with delivery of 15 liveborn infants. Four infants were of low birthweight (<2nd centile) but all have developed normally apart from one with behavioural/psychiatric problems. Three women had pre-existing cardiomyopathy prior to pregnancy. One of these women had deterioration of her cardiomyopathy during pregnancy and again in the post-partum period. Women with GSD III do not seem to have any issues with fertility. Overall the outcome of pregnancy for both mother and ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5279917 Tue, 27 Sep 2011 05:52:38 +0100 5279917 http://www.medworm.com/index.php?rid=5256077&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk60116n056645815%2F Content Type Journal ArticleCategory EditorialPages 1-2DOI 10.1007/s10545-011-9385-6Authors Timothy M. Cox, University of Cambridge, Cambridge, MA, 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=5256077 Thu, 22 Sep 2011 05:53:29 +0100 5256077 http://www.medworm.com/index.php?rid=5256078&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd75j081132375j55%2F Abstract  Cerebral micro- and macro-vasculopathy have been described in Fabry disease (FD). Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. We measured the hippocampus volumes in a group of clinically affected patients with FD and correlated the findings with the cognitive performance of the patients. Hippocampal volumes were determined manually on T1-weighted MR-images of 25 FD patients (age 36.5 ± 11.0 years) and 20 age-matched controls. Additionally, individual white matter (WM) and gray matter (GM) volumes were measured using brain segmentation ana... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5256078 Tue, 20 Sep 2011 05:50:18 +0100 5256078 http://www.medworm.com/index.php?rid=5256079&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc8j1560514232587%2F In conclusion, we identify individuals with 2 pathogenic mutations and those with only one heterozygous mutation in the residual activity range of 20-30%. Whereas heterozygosity is generally regarded as clinically irrelevant, identification of 2 VLCAD mutations leads to precautions in the management of the children. Based on our data we anticipate that individuals with a residual enzyme activity >20% present with a biochemical phenotype but likely remain asymptomatic throughout life. Studies in greater patient numbers are needed to correlate residual activities >10% with the genotype and the outcome. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s10545-011-9391-8Authors Lars Hoffmann, Department of General Pediatrics, University Children’s H... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5256079 Tue, 20 Sep 2011 05:50:16 +0100 5256079 http://www.medworm.com/index.php?rid=5231168&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1n05546061511763%2F Abstract  Alkaptonuria (AKU) is an autosomal recessive disorder due to homogentisate 1,2-dioxygenase (HGD) deficiency in the liver and characterized by a triad of signs, according to chronology of appearance: homogentisic aciduria (HGA ) or alkaptonuria, ochronosis then ochronotic arthropathy. This inborn error of metabolism is caused by mutations in the HGD gene. In this work we report observations of 96 AKU French patients from 81 families collected in the literature since 1882 and from our personal contribution since 1986, giving an incidence of the disease of around 1:680,000 (96/64.106). As expected for an autosomal recessive disorder the main findings of this study were: a slight predominance of males (51/93, 54,8%) over females (42/93, 45,2%), a strong predominance of... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5231168 Fri, 16 Sep 2011 16:43:41 +0100 5231168 http://www.medworm.com/index.php?rid=5231169&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7168092527332610%2F Abstract  In this case series we report 12 pregnancies, in women treated at four centres, illustrating some of the issues that may be encountered during pregnancy by women with inherited metabolic disease. We discuss how specific pregnancy, labour and delivery issues for mothers with methylmalonic acidemia, homocystinuria, propionic acidemia, glutaric acidemia type 1, ornithine transcarbamylase (OTC) deficiency and 3-hydroxy-3-methylglutaric(HMG)-CoA lyase deficiency were managed and the outcome for the mother and child in each case. Eight of the 12 pregnancies resulted in the successful delivery of a liveborn infant. Several women experienced decompensation of their condition during pregnancy or the post-partum period. There was one maternal death in a women with 3-hydroxy... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5231169 Wed, 14 Sep 2011 16:09:31 +0100 5231169 http://www.medworm.com/index.php?rid=5231170&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgn0604h84k385058%2F In conclusion, the Quick Motor Function Test can reliably rate clinical severity and motor function in children and adults with Pompe disease. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s10545-011-9388-3Authors Carine I. van Capelle, Department of Pediatrics, Division of Metabolic Diseases and Genetics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Postbus 2060, 3000 CB Rotterdam, the NetherlandsNadine A. M. E. van der Beek, Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the NetherlandsJuna M. de Vries, Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the NetherlandsPieter A.... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5231170 Mon, 12 Sep 2011 15:53:44 +0100 5231170 http://www.medworm.com/index.php?rid=5173384&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwnh4412tn6867p51%2F Abstract  Alkaptonuria (AKU) is a rare inborn error of metabolism associated with a deficient activity of homogentisate 1,2-dioxygenase (HGO), an enzyme involved in tyrosine and phenylalanine metabolism. Such a deficiency leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, where melanin-like pigments accumulate (ochronosis). Ochronosis involves especially joints, where an ochronotic arthropathy develops. Little is known on the molecular mechanisms leading to ochronosis and ochronotic arthropathy in AKU. Previous works of ours showed that HGA in vitro propagates oxidative stress through its conversion into benzoquinone acetate (BQA). We hence used an in vitro model consisting of human serum treated with HGA and ev... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5173384 Fri, 26 Aug 2011 16:23:30 +0100 5173384 http://www.medworm.com/index.php?rid=5173385&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm578nlu116j4083l%2F Abstract  Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5173385 Fri, 26 Aug 2011 16:23:29 +0100 5173385 http://www.medworm.com/index.php?rid=5167544&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe478p85781571527%2F Conclusions  Hearing impairment is common in MPS II. Early otolaryngological evaluation and intervention is recommended. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s10545-011-9378-5Authors Annerose Keilmann, Department of ORL, Langenbeckstr. 1 Gebäude 102, 55131 Mainz, GermanyTodsaporn Nakarat, Division of Communication Disorders, Department of ORL, University Medical Center, Mainz, GermanyIain A. Bruce, Department of Paediatric ORL, Royal Manchester Children’s Hospital, Manchester, UKDavid Molter, Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USAGunilla Malm, Department of Clinical Science, Intervention and Technology Division of Paediatrics, Karolinska University Hospital, Huddinge, 14186 Stock... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5167544 Wed, 24 Aug 2011 16:02:02 +0100 5167544 http://www.medworm.com/index.php?rid=5167547&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw58772r2qj3rhx48%2F We present two unrelated patients who presented with developmental delay and increased urinary concentrations of 3-hydroxyisobutyric acid. Both children were products of consanguineous unions and were of European or Pakistani descent. One patient developed a febrile illness and subsequently died from a hepatoencephalopathy at 2 years of age. Further studies were initiated and included tests of the HIBADH enzyme in fibroblast homogenates, which yielded normal activities. Sequencing of the ALDH6A1 gene (encoding methylmalonate semialdehyde dehydrogenase) suggested homozygosity for the missense mutation c.785 C > A (S262Y) in exon 7 which was not found in 210 control alleles. Mutation analysis of the ALDH6A1 gene of the second patient confirmed the presence of a differen... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5167547 Tue, 23 Aug 2011 15:50:54 +0100 5167547 http://www.medworm.com/index.php?rid=5167546&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe6105555727r0021%2F Abstract  Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whether the neutropenia is solely due to enhanced apoptosis of mature neutrophils or whether aberrant neutrophil development may also contribute. Here we demonstrate that hematopoietic progenitors from GSD-1b patients are not impaired in their capacity to develop into mature neutrophils. However, optimal survival of neutrophil progenitors from GSD-1b patients requires high glucose levels (> 200 mg dl−1), suggesting that even under normoglycemic conditions the... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5167546 Tue, 23 Aug 2011 15:50:54 +0100 5167546 http://www.medworm.com/index.php?rid=5167545&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn6l07353563t81w5%2F Content Type Journal ArticleCategory EditorialPages 1-2DOI 10.1007/s10545-011-9380-yAuthors Bridget Wilcken, The Children’s Hospital at Westmead, Sydney, Australia 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=5167545 Tue, 23 Aug 2011 15:50:54 +0100 5167545 http://www.medworm.com/index.php?rid=5167548&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd678166787q85223%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10545-011-9383-8Authors Victoria Manwaring, Enzyme and Metabolic Unit, Chemical Pathology, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH UKHelen Prunty, Enzyme and Metabolic Unit, Chemical Pathology, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH UKKatie Bainbridge, Enzyme and Metabolic Unit, Chemical Pathology, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH UKDerek Burke, Enzyme and Metabolic Unit, Chemical Pathology, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH UKNiamh Finnegan, Metabolic Department, Great Ormond Street Hospital for Children, 5th Floor, Southwood Building, Great Orm... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5167548 Tue, 23 Aug 2011 15:50:53 +0100 5167548 http://www.medworm.com/index.php?rid=5123623&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg31421h345844783%2F We describe a patient with a lethal mitochondrial encephalomyopathy due to a mtDNA deletion and no alterations in RARS2, whose magnetic resonance (MR) findings mimicked PCH6. A thorough diagnostic work-up for mitochondrial disorders should be carried out when facing with a PCH-like and severe white matter and basal ganglia involvement on brain MR imaging in children, even if clinical and laboratory mitochondrial “stigmata” are scant or nonspecific. Content Type Journal ArticlePages 1-3DOI 10.1007/s10545-011-9376-7Authors Roberta Biancheri, Child Neurology and Psychiatry Unit, G. Gaslini Pediatric Institute, Genova, ItalyClaudio Bruno, Muscular and Neurodegenerative Disease Unit, G. Gaslini Pediatric Institute, Genova, ItalyDenise Cassandrini, IRCCS Fondazione Stella Maris, P... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5123623 Mon, 08 Aug 2011 19:55:14 +0100 5123623 http://www.medworm.com/index.php?rid=5060840&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft125245480w72032%2F Conclusions  Taken together, these data do not support the hypothesis that galactosemia is a progressive neurodegenerative disease. However, greater attention to depression, anxiety, and social relationships may relieve the impact of this disorder in adults. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9372-yAuthors Susan E. Waisbren, Children’s Hospital Boston, Boston, MA, USANancy L. Potter, Washington State University, Pullman, WA, USACatherine M. Gordon, Children’s Hospital Boston, Boston, MA, USARobert C. Green, Boston University School of Medicine, Boston, MA, USAPatricia Greenstein, Beth Israel Deaconess Medical Center, Boston, MA, USACynthia S. Gubbels, Maastricht University Medical Center, Maastricht, NetherlandsEstela Rubio-Gozalbo, Maastr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5060840 Thu, 21 Jul 2011 18:05:34 +0100 5060840 http://www.medworm.com/index.php?rid=5060841&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh4252960j4731855%2F This article discusses these aspects in detail, and provides practical recommendations on how to optimize the gastrointestinal tolerability of miglustat. Content Type Journal ArticlePages 1-11DOI 10.1007/s10545-011-9368-7Authors Nadia Belmatoug, Reference Centre for Lysosomal Diseases, Beaujon Hospital, Clichy, FranceAlberto Burlina, Division of Metabolic Diseases, University Hospital Padova, Padova, ItalyPilar Giraldo, Miguel Servet Hospital, CIBERER, Zaragoza, SpainChris J. Hendriksz, Birmingham Children′s Hospital NHS Foundation Trust, Birmingham, UKDavid J. Kuter, Massachusetts General Hospital, Boston, MA, USAEugen Mengel, Villa Metabolica, University of Mainz, Mainz, GermanyGregory M. Pastores, Department of Neurology - Neurogenetics Unit, NYU Langone Medical Center, 403 Ea... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5060841 Thu, 21 Jul 2011 18:05:33 +0100 5060841 http://www.medworm.com/index.php?rid=5046477&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4754g31306x04524%2F Abstract  The biologist Lewis Thomas once wrote: “my mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me”. As humans, or indeed as any mammal, bird, or insect, we contain a specific molecular makeup that is driven by vast numbers of these miniscule powerhouses residing in most of our cells (mature red blood cells notwithstanding), quietly replicating, living independent lives and containing their own DNA. Everything we do, from running a marathon to breathing, is driven by these small batteries, and yet there is evidence that these molecular energy sources were originally bacteria, possibly parasitic, incorporated into our cells through symbiosis. Dys... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5046477 Thu, 14 Jul 2011 06:01:50 +0100 5046477 http://www.medworm.com/index.php?rid=5034496&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbn7215851p46j13h%2F Abstract  Increased circulating homogentisic acid in body fluids occurs in alkaptonuria (AKU) due to lack of enzyme homogentisate dioxygenase leading in turn to conversion of HGA to a pigmented melanin-like polymer, known as ochronosis. The tissue damage in AKU is due to ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, deploying nitisinone effectively requires its administration at the most optimal time in the natural history. AKU has a long apparent latent period before overt ochronosis develops. The rate of change of ochronosis and its consequences over time following its recognition has not been fully described in any quantitative manner. Two potential tools are described that were used to quantitate disease... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5034496 Tue, 12 Jul 2011 06:08:48 +0100 5034496 http://www.medworm.com/index.php?rid=5034497&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F34866415051431j1%2F Abstract  Combined methylmalonic acidemia and homocystinuria, cblC type, is stated to be the most common inborn error of intracellular cobalamin metabolism. The disorder can display a wide spectrum of clinical manifestations, spanning the prenatal period through late adulthood. While increased homocysteine concentrations and impaired methyl group metabolism may contribute to disease-related complications, the characteristic macular and retinal degeneration seen in many affected patients appears to be unique to cblC disease. The early detection of cblC disease by newborn screening mandates a careful assessment of therapeutic approaches and provides a new opportunity to improve the outcome of affected patients. The following article reviews the current knowledge on the compli... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5034497 Tue, 12 Jul 2011 06:08:47 +0100 5034497 http://www.medworm.com/index.php?rid=5034498&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F23r2w33g24w05704%2F This article reviews the biochemistry, clinical presentations, genotype-phenotype correlations, diagnosis and management of cblC disease. Content Type Journal ArticlePages 1-12DOI 10.1007/s10545-011-9364-yAuthors Nuria Carrillo-Carrasco, Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A18, Bethesda, MD 20892, USARandy J. Chandler, Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A18, Bethesda, MD 20892, USACharles P. Venditti, Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5034498 Tue, 12 Jul 2011 06:08:46 +0100 5034498 http://www.medworm.com/index.php?rid=5015871&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F27118550j1m62637%2F Abstract  Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied clinical manifestations mainly by a process of conversion of HGA to a polymeric melanin-like pigment known as ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, successful demonstration of its efficacy in modifying the natural history of AKU requires an effective quantitative assessment tool. We have described two potential tools that could be used to quantitate disease burden in AKU. One tool describes scoring the clinical features that includes clinical assessments, investigations and questionnaires in 15 patients with AKU. The second tool descr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5015871 Sat, 09 Jul 2011 06:12:17 +0100 5015871 http://www.medworm.com/index.php?rid=5015872&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh706u47j8664g4q2%2F Abstract  The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5015872 Sat, 09 Jul 2011 06:12:16 +0100 5015872 http://www.medworm.com/index.php?rid=5015873&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F16526857v1100266%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s10545-011-9370-0Authors Dirk J. Lefeber, Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Nijmegen, The NetherlandsEva Morava, Institute for Genetic and Metabolic Disease, Nijmegen, The NetherlandsJaak Jaeken, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium 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=5015873 Fri, 08 Jul 2011 06:29:59 +0100 5015873 http://www.medworm.com/index.php?rid=5015874&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpw3g4u22h10g3281%2F Abstract  In pilot studies of the usefulness of solid state nuclear magnetic resonance spectroscopy in characterizing chemical and molecular structural effects of alkaptonuria on connective tissue, we have obtained 13 C spectra from articular cartilage from an AKU patient. An apparently normal anatomical location yielded a cross polarization magic angle spinning spectrum resembling literature spectra and dominated by collagen and glycosaminoglycan signals. All spectral linewidths from strongly pigmented ochronotic cartilage however were considerably increased relative to the control indicating a marked increase in collagen molecular disorder. This disordering of cartilage structural protein parallels, at the atomic level, the disordering revealed at higher length scales by... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5015874 Thu, 07 Jul 2011 05:45:14 +0100 5015874 http://www.medworm.com/index.php?rid=5015876&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff03l06m621u07570%2F This study highlights the utility and biologic relevance of serum HCII-T levels in monitoring therapy in these disorders. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9369-6Authors Lorne Andrew Clarke, Department of Medical Genetics, The Child and Family Research Institute, University of British Columbia, 4500 Oak Street, RM C234, Vancouver, BC, Canada V6H-3N1Harmony Hemmelgarn, Department of Medical Genetics, The Child and Family Research Institute, University of British Columbia, 4500 Oak Street, RM C234, Vancouver, BC, Canada V6H-3N1Karen Colobong, Department of Medical Genetics, The Child and Family Research Institute, University of British Columbia, 4500 Oak Street, RM C234, Vancouver, BC, Canada V6H-3N1Anita Thomas, Department of Medical Genetics, The Child and ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=5015876 Wed, 06 Jul 2011 05:55:45 +0100 5015876 http://www.medworm.com/index.php?rid=5015875&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyp54j35427t73746%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10545-011-9366-9Authors Eva Morava, Department of Pediatrics, UMC Radboud Nijmegen, Nijmegen, The NetherlandsDirk Lefeber, Department of Pediatrics, UMC Radboud Nijmegen, 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=5015875 Wed, 06 Jul 2011 05:55:45 +0100 5015875 http://www.medworm.com/index.php?rid=4996722&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2l2411551277531%2F Abstract  Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria, ochronosis, and ochronotic arthritis. The defect is caused by mutations in the HGD gene, which maps to the human chromosome 3q21–q23. AKU shows a very low prevalence (1:100,000–250,000) in most ethnic groups, but there are countries such as Slovakia and the Dominican Republic in which the incidence of this disorder rises to as much as 1:19,000. In this work, we summarize the genetic aspects of AKU in general and the distribution of all known disease-causing mutations reported so far. We focus on special features of AKU in Slovakia, which is one of the countries with an increased incidence of this rare me... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4996722 Fri, 01 Jul 2011 05:42:35 +0100 4996722 http://www.medworm.com/index.php?rid=4966292&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy7w401915n2j62p0%2F Conclusions  MRI showed a typical spatial pattern, which evolved gradually and uniformly during disease progression in late-infantile MLD. In juvenile MLD MRI changes were already observed at disease onset and temporal patterns were more variable. As therapeutic options for MLD are evolving, these findings are not only important for patient counseling but also for the evaluation of therapeutic interventions. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9361-1Authors Samuel Groeschel, Department of Pediatric Neurology & Developmental Medicine and Experimental Pediatric Neuroimaging, University Children’s Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, GermanyChristiane Kehrer, Department of Pediatric Neurology & Developmental Medicine, University ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4966292 Wed, 22 Jun 2011 16:03:35 +0100 4966292 http://www.medworm.com/index.php?rid=4958400&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq1611862h2360123%2F Abstract  A high performance liquid chromatography method, adapted from an established urinary sugars method, has been developed for the analysis of a tetraglucose oligomer (Glc4) in urine. Pompe disease results from defects in the activity of lysosomal acid α-glucosidase (GAA) with patients typically excreting increased amounts of Glc4. Rapid determination of GAA in dried blood spots is now possible. However, enzymatic analysis is unable to discriminate between patients with Pompe disease and those individuals harbouring pseudo deficiency mutations. This method was able to quantify Glc4 levels in all patients analysed with an established diagnosis of Pompe disease, and all controls analysed had Glc4 levels below the limit of detection for this method. Importantly the method... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4958400 Mon, 20 Jun 2011 14:17:14 +0100 4958400 http://www.medworm.com/index.php?rid=4930337&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr152180g84785321%2F Conclusion  The bacterially expressed enzymes proved that the mutations found in patients and studied here indeed are detrimental. However, as in the case of red cell ASL activity assays, some mutations found in genetically homozygous patients with mild presentations resulted in virtual loss of enzyme activity in the bacterial system, suggesting a more protective environment for the mutant enzyme in the liver than in the heterologous expression system and/or in the highly dilute assays utilized here. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9357-xAuthors Katharina Engel, Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, 48149 Muenster, GermanyJean-Marc Vuissoz, Clinique de Pédiatrie, ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4930337 Sat, 11 Jun 2011 06:36:53 +0100 4930337 http://www.medworm.com/index.php?rid=4930338&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft932425122243168%2F We report here a series of six patients with severe CTP deficiency, four males and two females; clinical presentations include mild to severe mental retardation (6/6), associated with psychiatric symptoms (5/6: autistic behaviour, chronic hallucinatory psychosis), seizures (2/6) and muscular symptoms (2/4 males). Diagnosis was suspected upon elevated urinary creatine/creatinine (except in one of the female patients) and on a markedly decreased creatine peak on magnetic resonance spectroscopy (MRS). Diagnosis was confirmed by molecular analysis that identified four novel mutations not reported so far, including a mutation found twice in two male patients. All patients were treated successively and according to the same protocol by creatine alone then combined to its precursors, L-glyc... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4930338 Fri, 10 Jun 2011 06:34:13 +0100 4930338 http://www.medworm.com/index.php?rid=4900114&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0065104773789l42%2F Conclusions  Based on our findings we suggest that high priority treatments for rigorous effectiveness studies could include L-carnitine supplementation (MCAD and LCHAD/MTP deficiencies), restriction of dietary fat, and, for the long-chain disorders, feeding practices for breastfed infants and the use of various supplements (essential fatty acids, carbohydrates, cornstarch, multivitamins). Content Type Journal ArticlePages 1-9DOI 10.1007/s10545-011-9352-2Authors Beth K. Potter, Department of Epidemiology & Community Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, Canada K1H 8M5Julian Little, Department of Epidemiology & Community Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario, Canada K1H 8M5Pranesh Chakraborty, Newborn Screening Ontario ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900114 Wed, 01 Jun 2011 06:00:11 +0100 4900114 http://www.medworm.com/index.php?rid=4900115&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7398777h4367390%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s10545-011-9356-yAuthors Thomas Opladen, Division of Inborn Metabolic Diseases, University Children’s Hospital Heidelberg, Heidelberg, GermanyBettina Abu Seda, Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich, Zürich, SwitzerlandAnahita Rassi, Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich, Zürich, SwitzerlandBeat Thöny, Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich, Zürich, SwitzerlandGeorg F. Hoffmann, Division of Inborn Metabolic Diseases, University Children’s Hospital Heidelberg, Heidelberg, GermanyNenad Blau, Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich,... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900115 Mon, 30 May 2011 16:56:39 +0100 4900115 http://www.medworm.com/index.php?rid=4900116&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32743h6602767r55%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10545-011-9355-zAuthors Turgay Coşkun, Division of Pediatric Nutrition and Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey 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=4900116 Mon, 30 May 2011 16:56:36 +0100 4900116 http://www.medworm.com/index.php?rid=4900117&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flx00m246732823u8%2F Abstract  In 2007, the European Task Force for neuronopathic Gaucher disease (NGD) published a review of 55 patients across four countries. Although some observations were possible, analysis was difficult due to the absence of a systematic way of assessing patients. In response to this, a Severity Scoring Tool (SST) was devised to offer a systematic means of assessing the neurological presentation seen. The SST has been modified (mSST) and is a valid tool for monitoring neurological progression. This review describes disease status and progression of neurological manifestations in a cohort of 39 chronic NGD patients across three European countries over a period of 4 years, using the mSST. Content Type Journal ArticlePages 1-7DOI 10.1007/s10545-011-9347-zAuthors Elin H... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900117 Fri, 27 May 2011 18:16:03 +0100 4900117 http://www.medworm.com/index.php?rid=4900118&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9513n5834865414j%2F In conclusion, we report simple quantitative procedures to determine FSA in AFS and cultured fibroblasts improving both prenatal diagnostic efficacy for ISSD as well as confirmatory testing in cultured fibroblasts following initial screening in urine or AFS. Content Type Journal ArticlePages 1-5DOI 10.1007/s10545-011-9351-3Authors Jeroen van den Bosch, Department Clinical Genetics, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, The NetherlandsLinda F. Oemardien, Department Clinical Genetics, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, The NetherlandsMalgorzata I. Srebniak, Department Clinical Genetics, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, The NetherlandsMonique Piraud, Laboratoire des Maladies Héréditaires du Mé... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900118 Thu, 26 May 2011 16:08:18 +0100 4900118 http://www.medworm.com/index.php?rid=4900119&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyx74722k67656212%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10545-011-9353-1Authors Gregory M. Pastores, Departments of Neurology and Pediatrics, New York University School of Medicine, New York, 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=4900119 Thu, 26 May 2011 16:08:16 +0100 4900119 http://www.medworm.com/index.php?rid=4900120&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn7j7517119418371%2F Abstract  Despite the increase in the number of inherited metabolic diseases that can be detected at birth using a single dried blood spot sample, the impact of false positive results on parents remains a concern. We used an economic approach - the contingent valuation method – which asks parents to give their maximum willingness to pay for an extension in a screening programme and the degree to which the potential for false positive results diminishes their valuations. 160 parents of a child or children under the age of 16 years were surveyed and given descriptions of the current screening programme in the UK, an extended programme and an extended programme with no false positives. 148 (92.5%) respondents said they would accept the screen for the five extra conditio... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900120 Thu, 26 May 2011 16:08:08 +0100 4900120 http://www.medworm.com/index.php?rid=4900121&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv3h2m437738k3l31%2F Abstract  Lysosomal storage disorders (LSD) are monogenic diseases caused by the deficiency of different lysosomal enzymes that degrade complex substrates such as glycosaminoglycans, sphingolipids, and others. As a consequence there is multisystemic storage of these substrates. Most treatments for these disorders are based in the fact that most of these enzymes are soluble and can be internalized by adjacent cells via mannose-6-phosphate receptor. In that sense, these disorders are good candidates to be treated by somatic gene therapy based on cell microencapsulation. Here, we review the existing data about this approach focused on the LSD treatments, the advantages and limitations faced by these studies. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9350-... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900121 Wed, 25 May 2011 16:00:49 +0100 4900121 http://www.medworm.com/index.php?rid=4900122&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk12810416861880l%2F Abtract  N-linked glycosylation is one of the most abundant modifications of proteins in eukaryotic organisms. In the central reaction of the pathway, oligosaccharyltransferase (OST), a multimeric complex located at the membrane of the endoplasmic reticulum, transfers a preassembled oligosaccharide to selected asparagine residues within the consensus sequence asparagine-X-serine/threonine. Due to the high substrate specificity of OST, alterations in the biosynthesis of the oligosaccharide substrate result in the hypoglycosylation of many different proteins and a multitude of symptoms observed in the family of congenital disorders of glycosylation (CDG) type I. This review covers our knowledge of human OST and describes enzyme composition. The Stt3 subunit of OST harbors the... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900122 Wed, 25 May 2011 16:00:46 +0100 4900122 http://www.medworm.com/index.php?rid=4900124&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flm61110065u426g1%2F Abstract  Defects of the mitochondrial oxidative phosphorylation (OXPHOS) system are frequent causes of neurological disorders in children. Linkage analysis and DNA sequencing identified a new founder p.G250V substitution in the C20ORF7 complex I chaperone in five Ashkenazi Jewish patients from two families with a combined OXPHOS complex I and IV defect presenting with Leigh's syndrome in infancy. Complementation with the wild type gene restored complex I, but only partially complex IV activity. Although the pathogenic mechanism remains elusive, a C20ORF7 defect should be considered not only in isolated complex I deficiency, but also in combination with decreased complex IV. Given the significant 1:290 carrier rate for the p.G250V mutation among Ashkenazi Jews, this mutatio... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900124 Tue, 24 May 2011 05:52:17 +0100 4900124 http://www.medworm.com/index.php?rid=4900123&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl88207t48k7w5427%2F Conclusion  We postulate that imbalances in the expression of cell surface proteins necessary for activation, proliferation, and regulation of the intensity and duration of an immune response may result in defective T cell activation, proliferation, and effector functions in our model and potentially in human HIDS. Content Type Journal ArticlePages 1-10DOI 10.1007/s10545-011-9349-xAuthors Elizabeth J. Hager, Department of Biological Sciences, DOW ESE Room 742, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USAJon D. Piganelli, Division of Immunogenetics, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAHubert M. Tse, Department of Microbiology, Comprehensive Dia... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4900123 Tue, 24 May 2011 05:52:17 +0100 4900123 http://www.medworm.com/index.php?rid=4851585&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4m2w322643j7p820%2F Abstract  Sandhoff disease (SD) is a lysosomal disease caused by a mutation of the HEXB gene associated with excessive accumulation of GM2 ganglioside (GM2) in lysosomes and neurological manifestations. Production of autoantibodies against the accumulated gangliosides has been reported to be involved in the progressive pathogenesis of GM2 gangliosidosis, although the underlying mechanism has not been fully elucidated. The thymus is the key organ in the acquired immune system including the development of autoantibodies. We showed here that thymic involution and an increase in cell death in the organ occur in SD model mice at a late stage of the pathogenesis. Dramatic increases in the populations of Annexin-V+ cells and terminal deoxynucletidyl transferase dUTP nick end labelin... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4851585 Thu, 19 May 2011 16:36:48 +0100 4851585 http://www.medworm.com/index.php?rid=4838031&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8522247034439865%2F Abstract  Lysosomal storage disorders are inherited metabolic diseases in which a mutation in a gene encoding a lysosomal enzyme or lysosome-related protein results in the intra-cellular accumulation of substrate and reduced cell/tissue function. Few patients with neurodegenerative lysosomal storage disorders have access to safe and effective treatments although many therapeutic strategies have been or are presently being studied in vivo thanks to the availability of a large number of animal models. This review will describe the comparative advancement of a variety of therapeutic strategies through the ‘research pipeline’. Our goal is to provide information for clinicians, researchers and patients/families alike on the leading therapeutic candidates at this point in time... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4838031 Mon, 16 May 2011 15:48:33 +0100 4838031 http://www.medworm.com/index.php?rid=4826901&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj876808414v07002%2F We describe a single consanguineous family with three affected children exhibiting knee and/or hip pain associated with swelling. Detailed clinical evaluation demonstrated diffuse joint involvement with an unusual proliferative synovitis on MRI. Synovial biopsies were notable for an infiltration of macrophages with abundant cytoplasm filled with faintly basophilic vacuoles. We used homozygosity mapping with a panel of 262,000 single nucleotide polymorphism markers to identify a homozygous stretch of 40.52 Mb on chromosome 3p22.3 – 3p13 that segregated with the arthropathy in the family. Of the 378 genes in the interval, the three hyaluronoglucosaminidase genes were considered good candidates based on the phenotype. Dideoxy sequencing identified a homozygous deletion in HYAL1, ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4826901 Wed, 11 May 2011 06:25:59 +0100 4826901 http://www.medworm.com/index.php?rid=4818509&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh312748226g670j0%2F In conclusion, m.3243A > G mutation affects subcutaneous adipose tissue metabolism. This seems to occur before aberrant liver metabolism, if any, can be observed or before beta-cell failure results in mitochondrial diabetes. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9338-0Authors Markus M. Lindroos, Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, FIN-20521 Turku, FinlandRonald Borra, Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, FIN-20521 Turku, FinlandNina Mononen, Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, FinlandTerho Lehtimäki, Laboratory of Atherosclerosis Genetics, Department of C... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818509 Tue, 10 May 2011 06:03:37 +0100 4818509 http://www.medworm.com/index.php?rid=4818508&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frn8k5315j3402280%2F This study evaluates the relationship between intellectual outcome and concentration/variation in blood phenylalanine (Phe) during specific developmental periods (0–6 years, 7–12 years, >12 years) in our patients with PKU. Verbal comprehension, perceptual reasoning, and processing speed were used as measures of intelligence. Data were collected from 55 patients receiving treatment at the University of Utah Metabolic Clinic. Yearly median Phe levels increased and mean number of blood Phe samples decreased as patients aged. Yearly median blood Phe from 0–6 and 7–12 years were inversely associated with perceptual reasoning abilities using linear regression. Additionally, increased blood Phe concentration negatively impacted specific areas of verbal comprehension abilities for... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818508 Tue, 10 May 2011 06:03:37 +0100 4818508 http://www.medworm.com/index.php?rid=4818510&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq276jk327g587721%2F This study highlights the need for prospective experimental therapeutic research. Content Type Journal ArticlePages 1-7DOI 10.1007/s10545-011-9346-0Authors Jennifer Cialone, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USAErika F. Augustine, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USANicole Newhouse, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USAHeather Adams, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USAAmy Vierhile, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USAFrederick J. Marshall, University of Rochester, 601 Elmwood Ave, Box 631, Rochester, NY 14642, USAElisabeth A. de Blieck, University of Rochester, 601 Elmwood Ave, Box 63... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818510 Tue, 10 May 2011 06:03:36 +0100 4818510 http://www.medworm.com/index.php?rid=4818511&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F83522h4564770822%2F Conclusion  Our results suggest that genistein supplementation at 5 mg kg−1 day−1 did not improve disability estimated by using a particular scale. Content Type Journal ArticlePages 1-6DOI 10.1007/s10545-011-9342-4Authors Verónica Delgadillo, Neuropediatrics Department, Hospital Sant Joan de Déu, Barcelona, SpainMaria del Mar O’Callaghan, Neuropediatrics Department, Hospital Sant Joan de Déu, Barcelona, SpainRafael Artuch, Clinical Biochemistry Departament, Hospital Sant Joan de Déu, Barcelona, SpainRaquel Montero, Clinical Biochemistry Departament, Hospital Sant Joan de Déu, Barcelona, SpainMercedes Pineda, Neuropediatrics Department, Hospital Sant Joan de Déu, Barcelona, Spain Journal Journal of Inherited Metabolic DiseaseOnline ISSN... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818511 Tue, 10 May 2011 06:03:35 +0100 4818511 http://www.medworm.com/index.php?rid=4818512&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy63470841t16g201%2F Abstract  The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818512 Tue, 10 May 2011 06:03:34 +0100 4818512 http://www.medworm.com/index.php?rid=4818513&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F730u669302th7821%2F We describe our use of CGMS in a cohort of GSD patients, the results obtained and the frequency of complications. Our experience is that CGM is a reliable, well accepted and valid tool in the monitoring of GSD patients and allows for assessment of blood sugar control in the ‘real-life’ setting, unlike hospital admissions. Combining CGM with urine ketone and / or blood lactate measurements, again at home, improves the investigation yet further. It is possible to perform CGM for periods including both schooldays and weekends, and also to change the dietary regimen during the period of monitoring to reduce the frequency of assessments. Risks of decreased reliability in the low range of blood sugars may be outweighed by the increased validity of the patient being in the home environm... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4818513 Tue, 10 May 2011 06:03:33 +0100 4818513 http://www.medworm.com/index.php?rid=4793437&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk1t8665681835371%2F Abstract  Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in lif... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793437 Tue, 03 May 2011 16:03:56 +0100 4793437 http://www.medworm.com/index.php?rid=4793440&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2615462u7x2v65u1%2F Conclusion  These data highlight important differences in MPS I patients between Latin America and ROW in terms of phenotypic distribution, clinical manifestations, and treatment practices. Content Type Journal ArticlePages 1-9DOI 10.1007/s10545-011-9336-2Authors María Verónica Muñoz-Rojas, Genzyme do Brazil, Av. Francisco Matarazzo, 1400, Edifício Milano – 10° andar, 05001-903 São Paulo, SP, BrazilLuisa Bay, Unidad de Errores Congénitos del Metabolismo, Hospital Nacional de Pediatría J.P. Garrahan, Buenos Aires, ArgentinaLuz Sanchez, Pediatra y Neonatóloga, Hospital de Especialidades UMAE 25, Monterrey, MéxicoMarcel van Kuijck, Registry & Compassionate Use Programs, Genzyme, Latin America Group, Rio de Janeiro, BrazilSandra Ospina, Fundación Universitari... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793440 Tue, 03 May 2011 16:03:54 +0100 4793440 http://www.medworm.com/index.php?rid=4793439&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2148k8220678675%2F Abstract  Mitochondrial biogenesis is a complex process depending on both nuclear and mitochondrial DNA (mtDNA) transcription regulation to tightly coordinate mitochondrial levels and the cell’s energy demand. The energy requirements for a cell to support its metabolic function can change in response to varying physiological conditions, such as, proliferation and differentiation. Therefore, mitochondrial transcription regulation is constantly being modulated in order to establish efficient mitochondrial oxidative metabolism and proper cellular function. The aim of this article is to review the function of major protein factors that are directly involved in the process of mtDNA transcription regulation, as well as, the importance of mitochondrial nucleoid structure and its... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793439 Tue, 03 May 2011 16:03:54 +0100 4793439 http://www.medworm.com/index.php?rid=4793438&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa81370320q23j707%2F Abstract  Deficiency of phosphomannomutase (PMM2, MIM#601785) is the most common congenital disorder of glycosylation. Herein we report the genetic analysis of 22 Spanish PMM2 deficient patients and the functional analysis of 14 nucleotide changes in a prokaryotic expression system in order to elucidate their molecular pathogenesis. PMM2 activity assay revealed the presence of six protein changes with no enzymatic activities (p.R123Q, p.R141H, p.F157S, p.P184T, p.F207S and p.D209G) and seven mild protein changes with residual activities ranging from 16 to 54% (p.L32R, p.V44A p.D65Y, p.P113L p.T118S, p.T237M and p.C241S) and also one variant change with normal activity (p.E197A). The results obtained from Western blot analysis, degradation time courses of 11 protein changes ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793438 Tue, 03 May 2011 16:03:54 +0100 4793438 http://www.medworm.com/index.php?rid=4793441&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh73tg33j742594n1%2F Abstract  In Alpha-mannosidosis (MIM 248500) the patients accumulate mainly unbranched oligosaccharide chains in the lysosomes in all body tissues, including the brain. With ensuing therapeutic modalities in man (BMT and ERT) non-invasive methods of monitoring the effect of treatment are needed. Paramount is the possible effect of the treatment on the brain, since this organ is regarded as difficult to reach because of the blood-brain barrier. We therefore performed proton nuclear magnetic resonance spectroscopy (MRS) of the brain in two untreated patients, and a 16-year-old patient treated with BMT at the age of 10 to assess whether this non-invasive method could be applied in the monitoring of the accumulation of abnormal chemicals in the brain of patients. We found an ab... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793441 Tue, 03 May 2011 16:03:53 +0100 4793441 http://www.medworm.com/index.php?rid=4793443&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg28723u7717015hj%2F Abstract  Dopa decarboxylase (DDC or AADC) is a pyridoxal 5’-phosphate (PLP)-dependent enzyme that catalyzes the decarboxylation of L-aromatic amino acids into the corresponding aromatic amines. AADC deficiency is an inborn error of neurotransmitters biosynthesis with an autosomal recessive inheritance. About 30 pathogenic mutations have been identified, but the enzymatic phenotypes causing AADC deficiency are unknown, and the therapeutic management is challenging. Here, we report biochemical and bioinformatic analyses of the human wild-type DDC and the pathogenic variants G102S, F309L, S147R and A275T whose mutations concern amino acid residues at or near the active site. We found that the mutations cause, even if to different extents, a decreased PLP binding affinity (i... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793443 Tue, 03 May 2011 16:03:50 +0100 4793443 http://www.medworm.com/index.php?rid=4793442&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq846153473200h61%2F Abstract  Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous inborn errors of metabolism. At present, treatment is available for only one CDG, but potential treatments for the other CDG are on the horizon. It will be vitally important in clinical trials of such agents to have a clear understanding of both the natural history of CDG and the corresponding burden of disability suffered by patients. To date, no multicentre studies have attempted to document the natural history of CDG. This is in part due to the lack of a reliable assessment tool to score CDG’s diverse clinical spectrum. Based on our earlier experience evaluating disease progression in disorders of oxidative phosphorylation, we developed a practical and semi-quantitative r... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793442 Tue, 03 May 2011 16:03:50 +0100 4793442 http://www.medworm.com/index.php?rid=4793444&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp607w576841228h8%2F Abstract  Sixty-four children, aged 7 to 14 years, with early-treated PKU, were compared with control children on visual evoked potential (VEP) amplitudes and latencies and auditory mismatch negativity (MMN) amplitudes. It was further investigated whether indices of dietary control would be associated with these evoked potentials parameters. There were no significant differences between controls and children with PKU in VEP- and MMN-indices. However, higher lifetime Phe levels were, in varying degree and stronger than concurrent Phe level, related to increased N75 amplitudes, suggesting abnormalities in attention, and longer P110 latencies, indicating a reduction in speed of neural processing, possibly due to deficits in myelination or reduced dopamine levels in brain ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4793444 Tue, 03 May 2011 16:03:47 +0100 4793444 http://www.medworm.com/index.php?rid=4752078&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1t43g03m071j815%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s10545-011-9334-4Authors Wen Hwa Lee, Structural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ UKWyatt W. Yue, Structural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ UKEugene Raush, Molsoft LLC, San Diego, CA 92121, USAMaxim Totrov, Molsoft LLC, San Diego, CA 92121, USARuben Abagyan, Molsoft LLC, San Diego, CA 92121, USAUdo Oppermann, Structural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ UKBrian D. Marsden, Structural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ UK 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=4752078 Thu, 21 Apr 2011 06:04:12 +0100 4752078 http://www.medworm.com/index.php?rid=4752079&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0125345808016ht%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10545-011-9327-3Authors Cornelis Jakobs, VU University Medical Center, Amsterdam, 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=4752079 Thu, 21 Apr 2011 06:04:11 +0100 4752079 http://www.medworm.com/index.php?rid=4744482&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9p05l64877155638%2F Abstract  The cardiovascular manifestations of alkaptonuria relate to deposition of ochronotic pigment within heart valves, endocardium, aortic intima and coronary arteries. We assessed 16 individuals with alkaptonuria for cardiovascular disease, including full electrocardiographic and echocardiographic assessment. The self reported prevalence of valvular heart disease and coronary artery disease was low. There was a significant burden of previously undiagnosed aortic valve disease, reaching a prevalence of over 40% by the fifth decade of life. The aortic valve disease was found to increase in both prevalence and severity with advancing age. In contrast to previous reports, we did not find a significant burden of mitral valve disease or coronary artery disease. These findin... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4744482 Wed, 20 Apr 2011 06:08:09 +0100 4744482 http://www.medworm.com/index.php?rid=4744483&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp6u04216007337n7%2F This study stresses the insidious heterogeneous clinical onset of some cases of MNGIE, expands the spectrum of the phenotype, and suggests considering MNGIE in the differential diagnosis of enteropathic arthritis, isolated exercise intolerance, and inflammatory polyneuropathies not responsive to the usual treatment. A better understanding of the clinical heterogeneity of MNGIE is necessary in order to diagnose atypical cases and promote early diagnosis, which is now absolutely necessary in view of the new available therapies. Content Type Journal ArticlePages 1-5DOI 10.1007/s10545-011-9332-6Authors Massimiliano Filosto, Clinical Neurology, Section for Neuromuscular Diseases and Neuropathies, University Hospital Spedali Civili, Pz. le Spedali Civili 1, 25100 Brescia, ItalyMauro S... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4744483 Tue, 19 Apr 2011 07:16:26 +0100 4744483 http://www.medworm.com/index.php?rid=4730729&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj75p261662w51374%2F Abstract  In general, newborn screening is now a highly successful enterprise. The introduction of tandem mass spectrometry in the mid-1990s changed the pace of screening, raising its profile and increasing its relevance to a wider range of health professionals. The clinical effectiveness is not in doubt for some conditions, but is lacking for others. Evaluation has major difficulties for the rarer disorders and has been sadly neglected. Partly because clinical effectiveness has not been enthusiastically addressed, but also because of undue caution on the part of regulators, who often seem to ignore available evidence, there are huge differences in the adoption of screening programmes in different jurisdictions. New treatments, especially mutation-specific treatments, and t... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730729 Fri, 15 Apr 2011 15:49:16 +0100 4730729 http://www.medworm.com/index.php?rid=4730730&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr11k0068405n6846%2F Abstract  EXT1/EXT2-CDG (Multiple cartilagineous exostoses, hereditary multiple osteochondroma (MO); OMIM 133700/133701) are common defects of O-xylosylglycan glycosylation. The diagnostic criteria are at least two osteochondromas of the juxta-epiphyseal region of long bones with in the majority of cases a positive family history and/or mutation in one of the EXT genes. The authors report data on clinical symptoms and complications of 23 patients (from 16 families), discussing the family history, age of diagnosis, new clinical and molecular data. Fifteen mutations and large deletions, of which nine are new, were detected in the EXT1 and EXT2 gene by sequence analysis, FISH and MLPA analysis. Content Type Journal ArticlePages 1-5DOI 10.1007/s10545-011-9314-8Authors Mali... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730730 Fri, 15 Apr 2011 15:49:14 +0100 4730730 http://www.medworm.com/index.php?rid=4730731&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F117wp8k652106118%2F Conclusions  Adult Pompe disease is associated with a considerable burden of illness at both the societal and patient levels. The disease leads to substantial costs and dependency on medical devices, home care, and informal care, and has a high impact on the patient’s social network. In addition, patients are limited in their ability to work and have significantly reduced HRQoL. Content Type Journal ArticlePages 1-8DOI 10.1007/s10545-011-9320-xAuthors Tim A. Kanters, Department of Health Policy & Management, Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The NetherlandsMarloes L. C. Hagemans, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The NetherlandsNadine A. M. E. van der Bee... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730731 Fri, 15 Apr 2011 15:49:13 +0100 4730731 http://www.medworm.com/index.php?rid=4730732&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyr7255j55376q722%2F Conclusions  The rate of disease progression may be useful to diagnose vJNCL or cJNCL, which should be confirmed by molecular studies in CLN1/CLN3 genes. Further studies of genotype/phenotype correlation will be helpful for understanding the pathogenesis of this disease. Content Type Journal ArticlePages 1-11DOI 10.1007/s10545-011-9323-7Authors María-Socorro Pérez-Poyato, Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona, SpainMontserrat Milà Recansens, Biochemical and Molecular Genetics Department and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Hospi... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730732 Fri, 15 Apr 2011 15:49:12 +0100 4730732 http://www.medworm.com/index.php?rid=4730733&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4v72w753u88g5739%2F Conclusions  Neither a generally slower task performance nor distinctively altered functioning of brain networks involved in a task representing a subset of dopamine-dependent executive functions could be proven. Decreased accuracy and inconsistent findings in posterior areas necessitate further study of frontal-lobe functioning in PKU patients in larger study samples. Content Type Journal ArticlePages 1-11DOI 10.1007/s10545-011-9318-4Authors Benedikt Sundermann, Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str. 33, 48149 Muenster, GermanyBettina Pfleiderer, Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str. 33, 48149 Muenster, GermanyHarald E. Möller, Max Planck Institute for Human Cognitive a... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730733 Wed, 13 Apr 2011 15:59:01 +0100 4730733 http://www.medworm.com/index.php?rid=4730734&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu230391431301qn4%2F Abstract  Over the last 50 years, understanding the biochemical bases of glycogen storage disease type I has led to vastly improved survival and health outcomes but the management still centres around an extremely intensive dietary regimen. Patients’ metabolic profiles are really determined by the whole of the diet and it can be very difficult to adjust therapy accordingly. In an iso-energetic diet with reference total energy intake, high carbohydrate intake could compromise other macro- and micro-nutrients; if carbohydrates are not restricted then total energy intake is excessive. The quality of the macronutrient such as the glycemic index of carbohydrate, the type of sugar and the proportion of medium–chain triglyceride and essential fatty acids also has a bearin... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730734 Wed, 13 Apr 2011 15:59:00 +0100 4730734 http://www.medworm.com/index.php?rid=4730735&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3523t2217rq5384h%2F In conclusion, this study adds information on the natural course of PYCR1 deficiency and sheds light on the pathophysiology of this disorder. However, the exact pathogenesis of this new disorder and the role of proline in the development of the clinical phenotype remain to be fully explained. Content Type Journal ArticlePages 1-9DOI 10.1007/s10545-011-9319-3Authors Rita Kretz, Division of Metabolism, Kinderspital Zurich, Pediatric Research Centre (PRC), Steinwiesstrasse 75, 8032 Zurich, SwitzerlandBita Bozorgmehr, Kariminejad Najmabadi Pathology and Genetic Center, Tehran, IranMohamad Hasan Kariminejad, Kariminejad Najmabadi Pathology and Genetic Center, Tehran, IranMarianne Rohrbach, Division of Metabolism, Kinderspital Zurich, Pediatric Research Centre (PRC), Steinwiesstrasse 7... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730735 Tue, 12 Apr 2011 21:28:18 +0100 4730735 http://www.medworm.com/index.php?rid=4730736&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd81u177756v68715%2F Abstract  For more than a decade now blue native polyacrylamide gel electrophoresis (BN-PAGE) has been used for the study of the oxidative phosphorylation (OXPHOS) complexes. Catalytic activities of complexes I, II, IV and V can be assessed, after separation by gel electroforesis, by incubation of the BN-PAGE gel in specific staining solutions. However, until now, a reliable staining method for testing ubiquinol cytochrome c oxidoreductase (complex III) activity by BN-PAGE gel techniques was not available. In addition, spectrophotometric methods currently in use for detection of complex III deficiency in patients are not very sensitive. Here, we describe a newly developed diagnostic method for visualization of complex III activity by direct in-gel evaluation of ubiquinol cy... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4730736 Tue, 12 Apr 2011 05:48:46 +0100 4730736 http://www.medworm.com/index.php?rid=4708169&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl66lkm58q0r4212t%2F Abstract  Ketone bodies acetoacetate and 3-hydroxy-n-butyric acid are metabolites derived from fatty acids and ketogenic amino acids such as leucine. They are mainly produced in the liver via reactions catalyzed by the ketogenic enzymes mitochondrial 3-hydroxy-3-methylglutary-coenzyme A synthase and 3-hydroxy-3-methylglutary-coenzyme A lyase. After prolonged starvation, ketone bodies can provide up to two-thirds of the brain’s energy requirements. The rate-limiting enzyme of ketone body utilization (ketolysis) is succinyl-coenzyme A:3-oxoacid coenzyme A transferase. The subsequent step of ketolysis is catalyzed by 2-methylactoacetyl-coenzyme A thiolase, which is also involved in isoleucine catabolism. Inborn errors of metabolism affecting those four enzymes are presented a... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4708169 Fri, 08 Apr 2011 17:00:08 +0100 4708169 http://www.medworm.com/index.php?rid=4691467&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl45j33uv755u7730%2F Conclusions  The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment. Content Type Journal ArticlePages 1-18DOI 10.1007/s10545-011-9317-5Authors Renzo Manara, Neuroradiologic Unit, University Hospital of Padua, via Giustiniani 2, 35128 Padova, ItalyElena Priante, Centre for Rare Diseases, Department of Pediatrics, University of Padua, Padua, ItalyMarco Grimaldi, Neuroradiology Section, Department of Radiology, San Gerardo Hospital, Monza, ItalyLucia Santoro, Metabolic diseases, Institute of Maternal-Infantile Sciences, Polytechnic U... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4691467 Tue, 05 Apr 2011 09:59:19 +0100 4691467 http://www.medworm.com/index.php?rid=4662477&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F467g50238u865126%2F We examined GBA1 genotype, spleen status, Severity Score Index (SSI), and other patient characteristics as determinants of GD/PAH-HPS phenotype. We also examined the long-term outcomes of imiglucerase enzyme replacement therapy (ERT) +/− adjuvant therapies in 14 consecutive patients. We hypothesized a role of BMPR2 and ALK1 as genetic modifiers underlying GD/PAH-HPS phenotype. Median age at diagnosis of GD1 was 5 yrs (2–22); PAH was diagnosed at median 36 yrs (22–63). There was a preponderance of females (ratio 5:2). ERT was commenced at median 36.5 yrs (16–53) and adjuvant therapy at 36 yrs (24–57). GBA1 genotype was N370S homozygous in two patients, N370S heteroallelic in 12. Median SSI was 15 (7–20). All patients had undergone splenectomy at median a... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4662477 Tue, 29 Mar 2011 06:59:32 +0100 4662477 http://www.medworm.com/index.php?rid=4662478&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjm14262g81237775%2F Abstract  A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entire... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4662478 Tue, 29 Mar 2011 06:59:29 +0100 4662478 http://www.medworm.com/index.php?rid=4662479&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa44583405m723833%2F Abstract  Fumarate hydratase catalyzes the stereospecific hydration across the olefinic double bond in fumarate leading to L-malate. The enzyme is expressed in mitochondrial and cytosolic compartments, and participates in the Krebs cycle in mitochondria, as well as in regulation of cytosolic fumarate levels. Fumarate hydratase deficiency is an autosomal recessive trait presenting as metabolic disorder with severe encephalopathy, seizures and poor neurological outcome. Heterozygous mutations are associated with a predisposition to cutaneous and uterine leiomyomas and to renal cancer. The crystal structure of human fumarate hydratase shows that mutations can be grouped into two distinct classes either affecting structural integrity of the core enzyme architecture, or are loca... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4662479 Tue, 29 Mar 2011 06:59:28 +0100 4662479 http://www.medworm.com/index.php?rid=4635185&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbx75120854522860%2F We report a 31 year old woman who had prenatal carrier screening for Ashkenazi Jewish (AJ) genetic diseases and was found to have two acid ß-glucosidase (GBA) mutations, c.1226A>G(p.N370S) and c.1448T>C(p.L444P), consistent with the diagnosis of Type 1 Gaucher disease (GD1). This genotype typically manifests in late-adolescence with hepatosplenomegaly and early-onset bone involvement. The Proband had a normal physical examination, no organomegaly, and normal blood counts, skeletal survey, and bone density. Leukocyte acid ß-glucosidase and plasma chitotriosidase activities were normal. To investigate these unexpected results, her GBA alleles were RT-PCR amplified and sequenced. Five RT-PCR clones were negative for both mutations, while five clones had the c.1226A>G(p.N... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4635185 Tue, 22 Mar 2011 18:11:32 +0100 4635185 http://www.medworm.com/index.php?rid=4635186&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr65243769225l2lm%2F Abstract  Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be det... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4635186 Tue, 22 Mar 2011 18:11:30 +0100 4635186 http://www.medworm.com/index.php?rid=4635187&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F97vm56306g066687%2F Abstract  Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first geneti... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4635187 Tue, 22 Mar 2011 18:11:29 +0100 4635187 http://www.medworm.com/index.php?rid=4635188&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1757570086277813%2F Abstract  Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N-glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co-migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic pept... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4635188 Tue, 22 Mar 2011 18:11:28 +0100 4635188 http://www.medworm.com/index.php?rid=4614221&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6337421n13002804%2F In this study, we generated affinity-purified polyclonal antibody against murine MMR and used it to carry out a systematic examination of MMR protein localization in murine models of Gaucher, Niemann-Pick, Fabry, and Pompe diseases. Using immunohistochemistry, immunofluorescence, and confocal microscopy, we examined MMR distribution in liver, spleen, lung, kidney, heart, diaphragm, quadriceps, and triceps in these animal models and compared them with MMR distribution in wild-type mice. Content Type Journal ArticlePages 1-15DOI 10.1007/s10545-011-9285-9Authors Xin Sheen Zhang, Department of Pathology, Genzyme Corporation, 5 The Mountain Road, Framingham, MA 01701 USAWilliam Brondyk, Department of New Protein Therapeutics, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4614221 Thu, 17 Mar 2011 18:12:35 +0100 4614221 http://www.medworm.com/index.php?rid=4614222&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdg16j6h8903vk28j%2F We present the first reported case of B12 non-responsive methylmalonic acidaemia due to MMAB mutation to undergo an isolated renal transplant for renal failure. At 8 years of age he was listed for a combined liver and kidney transplant following progressive renal impairment. His metabolic control deteriorated with declining renal function and he was commenced on haemodialysis, leading to marked symptomatic and biochemical improvement. He was therefore relisted for isolated cadaveric renal transplant instead. He underwent successful renal transplantation at 12 years of age and now 6 years post transplant he is enjoying a more normal lifestyle with a marked reduction in plasma methylmalonate. Content Type Journal ArticlePages 1-6DOI 10.1007/s10545-011-9303-yAuthors ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4614222 Thu, 17 Mar 2011 18:12:34 +0100 4614222 http://www.medworm.com/index.php?rid=4614224&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4682068155443155%2F Conclusion  Stem cell transplantation does not halt the progression of a large range of disabling musculoskeletal abnormalities in Hurler’s disease. Although prospective data on the quantification, progression and treatment of these deformities were very limited, early surgical intervention is often advocated. Prospective data collection will be mandatory to achieve better evidence on the effect of treatment strategies. Content Type Journal ArticlePages 1-13DOI 10.1007/s10545-011-9304-xAuthors Marleen H. van der Linden, Department of Orthopaedics, University Medical Center Utrecht, HP G 05.228, Postbus 85500, 3508 GA Utrecht, The NetherlandsMoyo C. Kruyt, Department of Orthopaedics, University Medical Center Utrecht, HP G 05.228, Postbus 85500, 3508 GA Utrecht, Th... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4614224 Thu, 17 Mar 2011 18:12:33 +0100 4614224 http://www.medworm.com/index.php?rid=4614223&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv0p87w2k7r37ux24%2F Abstract  Mucopolysaccharidosis I Hurler (MPS IH) is a progressive multisystemic disorder caused by alpha-L-iduronidase deficiency. First choice of treatment in MPS IH children is haematopoietic stem cell transplantation (HSCT). The effect of HSCT has been shown to have limited influence on skeletal manifestations by poor penetration of musculoskeletal tissues by the enzyme derived from donor leucocytes. Aim of this study was to investigate the effect of HSCT on the craniocervical junction (CCJ) in Hurler patients. We analysed retrospectively sequential magnetic resonance imaging (MRI) scans of 30 patients with Hurler disease treated by HSCT since 1982 at the Royal Manchester Children’s Hospital, UK, in order to determine whether the patients suffer from dens hypoplasia. ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4614223 Thu, 17 Mar 2011 18:12:33 +0100 4614223 http://www.medworm.com/index.php?rid=4614225&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkhh1n534hrj50426%2F Abstract  In every newborn with even mild hyperphenylalaninemia (HPA) tetrahydrobiopterin (BH4) deficiencies need to be excluded as soon as possible. Differential diagnosis is most commonly performed by analysis of urinary neopterin and biopterin. In 2005 a new method for the measurement of neopterin, biopterin and other pterins in dried blood spot (DBS) on filter paper was introduced. In order to evaluate the usefulness of this method as a standard tool for differential diagnosis of HPAs we analyzed neopterin, biopterin, pterin and dihydropteridine reductase activity in DBS from 362 patients with HPA over the period of five years. Age-dependent reference values were established for the HPA population. Sixty-four patients with BH4 deficiency (27 patients with 6-pyruvoyl-tetr... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4614225 Thu, 17 Mar 2011 18:12:32 +0100 4614225 http://www.medworm.com/index.php?rid=4577596&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj5u745j1776333x9%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s10545-011-9310-zAuthors Gerard T. Berry, Division of Genetics, Children’s Hospital Boston, Harvard Medical School, Center for Life Sciences Building, Room 14070 3 Blackfan Circle, Boston, MA 02115, 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=4577596 Thu, 10 Mar 2011 17:11:20 +0100 4577596 http://www.medworm.com/index.php?rid=4577597&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk67856812w6164rh%2F Abstract  Contribution of mass spectrometry (MS) in the diagnosis and characterization of congenital disorders of glycosylation (CDG) has long been known. CDG type I diseases are characterized by the under-occupancy of protein N-glycosylation sites. Electrospray (ESI) MS and matrix assisted laser desorption ionization (MALDI) MS are effective for underglycosylation analyses of intact serum Transferrin (Tf) in CDG-I patients by mass determination of individual component glycoforms. Thus, high-throughput methods developed to speed-up analytical times found increasing application in clinical testing for CDG detection. ESI MS recognizable glycoform profiles of serum Tf have been reported in CDG-I different from PMM2-CDG and in individual CDG-II defects. MALDI MS analysis of aci... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4577597 Tue, 08 Mar 2011 06:43:23 +0100 4577597 http://www.medworm.com/index.php?rid=4577599&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkk9241v7u164l186%2F Abstract  Congenital disorders of glycosylation (CDG) is a booming class of metabolic diseases. Its number has increased nearly fourfold (to 45) since 2003, the year of the Komrower lecture, entitled ‘Congenital disorders of glycosylation CDG): It’s all in it!’. This paper presents an overview of recently discovered CDG and CDG phenotypes, of a diagnostic approach, of (the lack of) treatment, of CDG genetics, of a novel CDG nomenclature and classification, and of some future directions in the CDG field. Content Type Journal ArticlePages 1-6DOI 10.1007/s10545-011-9299-3Authors Jaak Jaeken, Universitair Ziekenhuis Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4577599 Tue, 08 Mar 2011 06:43:21 +0100 4577599 http://www.medworm.com/index.php?rid=4577598&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk388482qh96p5242%2F This study aims to determine the presence of neurological symptoms (NS) and Parkinson’s disease (PD) in Spanish GD patients and their relatives. We surveyed 87 GD Spanish families and validated the information obtained on the neurological involvement through their physicians, as well as the historical data included in the Spanish Gaucher Disease Registry. Neurological abnormalities were correlated with the genetic characteristics. Statistical analyses included descriptive parameters, ANOVA, t-test, correlation study and Pearson coefficient. Information was obtained from 118 patients and 324 relatives. Out of 110 patients with type 1 GD, 32 (29.1%) reported NS and 7 (6.4%) had PD. In relatives, a total of 39 (13.1%) subjects had NS, including 16 with PD (5.3%). The prevalence of NS ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4577598 Tue, 08 Mar 2011 06:43:21 +0100 4577598 http://www.medworm.com/index.php?rid=4577600&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk8m5336744t32423%2F Abstract  Polyisoprenoid alcohols are membrane lipids that are present in every cell, conserved from archaea to higher eukaryotes. The most common form, alpha-saturated polyprenol or dolichol is present in all tissues and most organelle membranes of eukaryotic cells. Dolichol has a well defined role as a lipid carrier for the glycan precursor in the early stages of N-linked protein glycosylation, which is assembled in the endoplasmic reticulum of all eukaryotic cells. Other glycosylation processes including C- and O-mannosylation, GPI-anchor biosynthesis and O-glucosylation also depend on dolichol biosynthesis via the availability of dolichol-P-mannose and dolichol-P-glucose in the ER. The ubiquity of dolichol in cellular compartments that are not involved in glycosylation ... Journal of Inherited Metabolic Disease journals http://www.medworm.com/rss/comments.php?id=4577600 Tue, 08 Mar 2011 06:43:19 +0100 4577600 http://www.medworm.com/index.php?rid=4558251&cid=s_35991_49_f&fid=35991&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk576886413t3wq37%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10545-011-9293-9Authors Bernhard Rupp, k.k. Hofkristallamt, Livermore, CA 94551, 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=4558251 Thu, 03 Mar 2011 08:47:14 +0100 4558251