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This page shows you the latest news and research items in this category.

Diurnal variation of phenylalanine and tyrosine concentrations in adult patients with phenylketonuria: subcutaneous microdialysis is no adequate tool for the determination of amino acid concentrations
Conclusions: Slight diurnal variation of phenylalanine concentrations in serum implicates that a single blood sample does reliably reflect the metabolic control in this group of adult patients. Phenylalanine concentrations determined by subcutaneous microdialysis do not correlate with the patients' phenylalanine concentrations in serum/blood. (Source: Nutrition Journal)
Source: Nutrition Journal - May 14, 2013 Category: Nutrition Authors: Sarah GrünertCorinna BrichtaAndreas KrebsHans-Willi ClementReinhold RauhChristian FleischhakerKlaus HennighausenJörn SassK Schwab Source Type: research

Tetrahydrobiopterin, its Mode of Action on Phenylalanine Hydroxylase, and Importance of Genotypes for Pharmacological Therapy of Phenylketonuria
ABSTRACT In about 20%–30% of phenylketonuria (PKU) patients (all phenotypes of PAH deficiency), Phe levels may be controlled through phenylalanine hydroxylase cofactor tetrahydrobiopterin therapy. These patients can be diagnosed by an oral tetrahydrobiopterin challenge and are characterized by mutations coding for proteins with substantial residual PAH activity. They can be treated with a commercially available synthetic form of tetrahydrobiopterin, either as a monotherapy or as adjunct to the diet. This review article summarizes molecular and metabolic bases of PKU and the importance of the tetrahydrobiopterin loading t...
Source: Human Mutation - May 1, 2013 Category: Genetics & Stem Cells Authors: Caroline Heintz, Richard G.H. Cotton, Nenad Blau Tags: Review Source Type: research

Nutrition education tools used in phenylketonuria: clinician, parent and patient perspectives from three international surveys
ConclusionsThere was a discrepancy between clinicians and patient views regarding the perceived effectiveness of the nutrition education tools. Future research is needed surrounding the impact nutrition education may have on improved dietary compliance in patients with PKU. (Source: Journal of Human Nutrition and Dietetics)
Source: Journal of Human Nutrition and Dietetics - April 23, 2013 Category: Nutrition Authors: L. E. Bernstein, J. R. Helm, J. C. Rocha, M. F. Almeida, F. Feillet, R. M. Link, M. Gizewska Tags: Research Paper Source Type: research

Evolution of the neonatal screening program in the state of Tocantins
CONCLUSION: Although there have been great developments in neonatal screening program in this state, there is need for greater government incentives to optimize the program and to make the PNTN advance to its next phases. (Source: Arquivos Brasileiros de Endocrinologia e Metabologia)
Source: Arquivos Brasileiros de Endocrinologia e Metabologia - April 13, 2013 Category: Endocrinology Source Type: research

Tetrahydrobiopterin, its Mode of Action on Phenylalanine Hydroxylase and Importance of Genotypes for Pharmacological Therapy of Phenylketonuria
ABSTRACT In about 20–30% of phenylketonuria patients (all phenotypes of PAH deficiency), Phe levels may be controlled through phenylalanine hydroxylase cofactor tetrahydrobiopterin therapy. These patients can be diagnosed by an oral tetrahydrobiopterin challenge and are characterized by mutations coding for proteins with substantial residual PAH activity. They can be treated with a commercially available synthetic form of tetrahydrobiopterin, either as a monotherapy or as adjunct to the diet. This review article summarizes molecular and metabolic bases of phenylketonuria and the importance of the tetrahydrobiopterin load...
Source: Human Mutation - April 4, 2013 Category: Genetics & Stem Cells Authors: Caroline Heintz, Richard G.H. Cotton, Nenad Blau Tags: Review Source Type: research

Body mass index in adult patients with diet‐treated phenylketonuria
ConclusionsThe number of overweight and obese patients with diet‐treated PKU in the UK is a concern. This could lead to other obesity‐related complications increasing the complexity of diet and the cost of their care. There is a need to educate patients with respect to adopting a healthy, low phenylalanine diet and lifestyle to prevent further rises in BMI. (Source: Journal of Human Nutrition and Dietetics)
Source: Journal of Human Nutrition and Dietetics - April 3, 2013 Category: Nutrition Authors: L. V. Robertson, N. McStravick, S. Ripley, E. Weetch, S. Donald, S. Adam, A. Micciche, S. Boocock, A. MacDonald Tags: Research Paper Source Type: research

Quality of life among parents of children with phenylketonuria (PKU)
This study was designed to evaluate the parental quality of life (PQoL) of parents of children and adolescents who have PKU and identify possible predictors of PQoL. Methods: In this cross-sectional study 89 parents completed self-report measures of PQoL, family stress, social support, and parental coping. To determine the impact of these potential predictors on PQoL, regression and mediation analyses were performed. Results: Most parents coped well with their children’s metabolic disorder. Family stress (β = −0.42; p (Source: Health and Quality of Life Outcomes)
Source: Health and Quality of Life Outcomes - March 28, 2013 Category: Global & Universal Authors: Astrid FidikaChristel SalewskiLutz Goldbeck Source Type: research

Molecular analysis of exons 6 and 7 of phenylalanine hydroxylase gene mutations in Phenylketonuria patients in Western Iran
Conclusion: The frequency of R261X, the most common mutation in our study, in Iranian population is <5%. Furthermore, there is no report of detection of R176X and R243Q in Isfahan and Azeri Turkish populations. These findings confirm the common Mediterranean mutations in this local population, although with more or lower frequencies than those reported in other related studies in Iran. Therefore, it may be necessary to study the PAH gene mutations in other provinces of Iran separately. (Source: Indian Journal of Human Genetics)
Source: Indian Journal of Human Genetics - March 4, 2013 Category: Genetics & Stem Cells Authors: Keyvan MoradiReza AlibakhshiKeyghobad GhadiriSaeid Reza KhatamiHamid Galehdari Source Type: research

Testing for Tetrahydrobiopterin Responsiveness in Patients with Hyperphenylalaninemia due to Phenylalanine Hydroxylase Deficiency.
CONCLUSION: The arbitrary responsiveness definition of a >30% reduction in blood phenylalanine appears to be a good compromise between sensitivity and specificity for the initial screening test. However, individual patient characteristics should be considered when interpreting results, especially in patients with low baseline phenylalanine levels. PMID: 23436109 [PubMed - as supplied by publisher] (Source: Advances in Therapy)
Source: Advances in Therapy - February 20, 2013 Category: Drugs & Pharmacology Authors: Cerone R, Andria G, Giovannini M, Leuzzi V, Riva E, Burlina A Tags: Adv Ther Source Type: research

Karl Blau obituary
iOur friend and former colleague, Karl Blau, who has died aged 84, was a talented and internationally respected biochemist. In 1966, Karl was invited to take charge of a laboratory at the North Carolina School of Medicine in Chapel Hill, where he published important early studies on the metabolites produced by children with inherited metabolic diseases, particularly phenylketonuria.In 1972, he established one of the UK's first prenatal diagnostic laboratories for inherited diseases, at Queen Charlotte's maternity hospital in London. Karl developed a particular interest in the prenatal diagnosis of cystic fibrosis; in the e...
Source: Guardian Unlimited Science - February 19, 2013 Category: Science Tags: Obituaries Biology guardian.co.uk Chemistry Biochemistry and molecular biology Science From the Guardian Source Type: news

A magnetic nanoparticles-zinc oxide/zinc hexacyanoferrate hybrid film for amperometric determination of tyrosine.
Abstract A method is described for the construction of a highly sensitive amperometric sensor for the detection of tyrosine, employing a magnetic nanoparticles-zinc oxide/zinc hexacyanoferrate (Fe(3)O(4)NP-ZnO/ZnHCF) hybrid film electrodeposited on the surface of a Pt electrode as working electrode. The sensor is based on electrocatalytic mechanism initiated by electrochemical oxidation of the reduced form of the hybrid film at +0.2 V vs. Ag/AgCl followed by completion of chemical oxidation of tyrosine. The sensor showed optimum response within 2 s at pH 2. The working/linear range of the sensor was 0.02-2.76 mM...
Source: Bioprocess and Biosystems Engineering - February 15, 2013 Category: Biomedical Engineering Authors: Narang J, Chauhan N, Pundir S, Pundir CS Tags: Bioprocess Biosyst Eng Source Type: research

Newborn screening of phenylketonuria using direct analysis in real time (DART) mass spectrometry.
Abstract Phenylketonuria (PKU) is commonly included in the newborn screening panel of most countries, with various techniques being used for quantification of L-phenylalanine (Phe). To diagnose PKU as early as possible in newborn screening, a rapid and simple method of analysis was developed. Using direct analysis in real time (DART) ionization coupled with triple-quadrupole tandem mass spectrometry (TQ-MS/MS) and with use of a 12 DIP-it tip scanner autosampler in positive ion mode, we analyzed dried blood spot (DBS) samples from PKU newborns. The concentration of Phe was determined using multiple reaction monitori...
Source: Analytical and Bioanalytical Chemistry - February 10, 2013 Category: Chemistry Authors: Wang C, Zhu H, Cai Z, Song F, Liu Z, Liu S Tags: Anal Bioanal Chem Source Type: research

Genes and Civil Liberties
Conclusion Although human genetics research and development are usually presented as “advances,” they may also be setting back our civil liberties on many fronts. Chief among the downsides are increased numbers of widely-available databases that correlate many facets of people’s biology, lives, and activities, as well as increasing incidences of loss of privacy and discrimination. While federal legislation and administrative rules have begun to address these problems, private and governmental data mining grows rapidly as new technological formats are developed and a technological rationality (i.e., ̶...
Source: ActionBioscience - January 30, 2013 Category: Biology Authors: Ali Hochberg Source Type: news

Genes and Civil Liberties
Conclusion Although human genetics research and development are usually presented as “advances,” they may also be setting back our civil liberties on many fronts. Chief among the downsides are increased numbers of widely-available databases that correlate many facets of people’s biology, lives, and activities, as well as increasing incidences of loss of privacy and discrimination. While federal legislation and administrative rules have begun to address these problems, private and governmental data mining grows rapidly as new technological formats are developed and a technological rationality (i.e., “...
Source: ActionBioscience - January 30, 2013 Category: Biology Authors: Ali Hochberg Source Type: news

Genes and Civil Liberties
Conclusion Although human genetics research and development are usually presented as “advances,” they may also be setting back our civil liberties on many fronts. Chief among the downsides are increased numbers of widely-available databases that correlate many facets of people’s biology, lives, and activities, as well as increasing incidences of loss of privacy and discrimination. While federal legislation and administrative rules have begun to address these problems, private and governmental data mining grows rapidly as new technological formats are developed and a technological rationality (i.e., ̶...
Source: ActionBioscience - January 30, 2013 Category: Science Authors: Ali Hochberg Source Type: news

BioMarin seeks to test enzyme-replacement therapy in Batten Disease patients
BioMarin Pharmaceutical Inc. doesn't back down from a tough rare disease. The Novato company (NASDAQ: BMRN), which made its name with enzyme-replacement therapies that tackle virtually unpronounceable orphan diseases like phenylketonuria and versions of mucopolysaccharidosis, expects to enroll the first patient by mid-year in an early-stage clinical trial in Batten Disease. CEO Jean-Jacques Bienaimé said BioMarin will file an investigational new drug application with the Food and Drug Administration… (Source: bizjournals.com Health Care:Hospitals headlines)
Source: bizjournals.com Health Care:Hospitals headlines - January 22, 2013 Category: Hospital Management Authors: Ron Leuty Source Type: research

BioMarin seeks to test enzyme-replacement therapy in Batten Disease patients
BioMarin Pharmaceutical Inc. doesn't back down from a tough rare disease. The Novato company (NASDAQ: BMRN), which made its name with enzyme-replacement therapies that tackle virtually unpronounceable orphan diseases like phenylketonuria and versions of mucopolysaccharidosis, expects to enroll the first patient by mid-year in an early-stage clinical trial in Batten Disease. CEO Jean-Jacques Bienaimé said BioMarin will file an investigational new drug application with the Food and Drug Administration… (Source: bizjournals.com Health Care:Biotechnology headlines)
Source: bizjournals.com Health Care:Biotechnology headlines - January 22, 2013 Category: Biotechnology Authors: Ron Leuty Source Type: research

Is Melatonin Synthesis a New Biomarker for the Pathogenesis and Treatment of Phenylketonuria?
More than 30 years ago, Charles Scriver and Carol Clow described phenylketonuria (PKU) as the epitome of biochemical genetics, the disorder from which much of our model for diagnosing, treating, and understanding inborn errors has derived. They placed PKU at this pinnacle because it was the disorder among the inborn errors in which the clinical biochemistry, the clinical effects, the enzymatic deficiency, the involvement of an endogenously synthesized cofactor, its genetic heterogeneity, and a number of other features had been described. (Source: The Journal of Pediatrics)
Source: The Journal of Pediatrics - January 14, 2013 Category: Pediatrics Authors: Stephen Cederbaum, Harvey L. Levy Tags: Editorials Source Type: research

A new model for allosteric regulation of phenylalanine hydroxylase: Implications for disease and therapeutics.
Abstract The structural basis for allosteric regulation of phenylalanine hydroxylase (PAH), whose dysfunction causes phenylketonuria (PKU), is poorly understood. A new morpheein model for PAH allostery is proposed to consist of a dissociative equilibrium between two architecturally different tetramers whose interconversion requires a ∼90° rotation between the PAH catalytic and regulatory domains, the latter of which contains an ACT domain. This unprecedented model is supported by in vitro data on purified full length rat and human PAH. The conformational change is both predicted to and shown to render the tetram...
Source: Archives of Biochemistry and Biophysics - January 10, 2013 Category: Biochemistry Authors: Jaffe EK, Stith L, Lawrence SH, Andrake M, Dunbrack RL Tags: Arch Biochem Biophys Source Type: research

Phenylalanine hydroxylase misfolding and pharmacological chaperones.
Abstract Phenylketonuria (PKU) is a loss-of-function inborn error of metabolism. As many other inherited diseases the main pathologic mechanism in PKU is an enhanced tendency of the mutant phenylalanine hydroxylase (PAH) to misfold and undergo ubiquitin-dependent degradation. Recent alternative approaches with therapeutic potential for PKU aim at correcting the PAH misfolding, and in this respect pharmacological chaperones are the focus of increasing interest. These compounds, which often resemble the natural ligands and show mild competitive inhibition, can rescue the misfolded proteins by stimulating their renatu...
Source: Current Topics in Medicinal Chemistry - January 4, 2013 Category: Chemistry Authors: Underhaug J, Aubi O, Martinez A Tags: Curr Top Med Chem Source Type: research

Cofactors and metabolites as protein folding helpers in metabolic diseases.
Abstract In the past few decades, improved early diagnosis methods, technological developments and an increasing crosstalk between clinicians and researchers has led to the identification of an increasing number of inborn metabolic diseases. In these disorders, missense mutations are the most frequent type of genetic defects, frequently resulting in defective protein folding. A better understanding at the molecular level of protein misfolding and its role in disease has prompted the emergence of therapies based in the use of small molecules that have the ability to correct protein folding defects. Well-known cases ...
Source: Current Topics in Medicinal Chemistry - January 4, 2013 Category: Chemistry Authors: Rodrigues JV, Henriques BJ, Lucas TG, Gomes CM Tags: Curr Top Med Chem Source Type: research

Mutations of the phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi, China
The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, where...
Source: Genetics and Molecular Biology - December 15, 2012 Category: Genetics & Stem Cells Source Type: research

Role of Catalase and Superoxide Dismutase Activities on Oxidative Stress in the Brain of a Phenylketonuria Animal Model and the Effect of Lipoic Acid.
Abstract Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7...
Source: Cellular and Molecular Neurobiology - December 12, 2012 Category: Cytology Authors: Moraes TB, Jacques CE, Rosa AP, Dalazen GR, Terra M, Coelho JG, Dutra-Filho CS Tags: Cell Mol Neurobiol Source Type: research

Spectrum of mutations in Lebanese patients with phenylalanine hydroxylase deficiency.
Abstract Phenylketonuria is an autosomal recessive inborn error of metabolism resulting from phenylalanine hydroxylase deficiency. Genetic basis of phenylalanine hydroxylase deficiency has been reported in various European and Asian countries with few reports available in Arab populations of the Mediterranean region. This is the first pilot study describing phenotype and genotype of 23 Lebanese patients with phenylketonuria. 48% of the patients presented mainly with neurological signs at a mean age of 2years 9months, as newborn screening is not yet a nationwide policy. 56.5% of the patients had classical phenylketo...
Source: Gene - December 3, 2012 Category: Genetics & Stem Cells Authors: Karam PE, Al-Hamra RS, Nemer G, Usta J Tags: Gene Source Type: research

Patterns of Brain Injury in Inborn Errors of Metabolism
Many inborn errors of metabolism (IEMs) are associated with irreversible brain injury. For many, it is unclear how metabolite intoxication or substrate depletion accounts for the specific neurologic findings observed. IEM-associated brain injury patterns are characterized by whether the process involves gray matter, white matter, or both, and beyond that, whether subcortical or cortical gray matter nuclei are involved. Despite global insults, IEMs may result in selective injury to deep gray matter nuclei or white matter. This manuscript reviews the neuro-imaging patterns of neural injury in selected disorders of metabolism...
Source: Seminars in Pediatric Neurology - December 1, 2012 Category: Neurology Authors: Andrea L. Gropman Source Type: research

Large Neutral Amino Acid Supplementation Increases Melatonin Synthesis in Phenylketonuria: A New Biomarker
Objective: To determine whether levels of melatonin in blood and urine can serve as a peripheral biomarker to reflect brain serotonin synthesis in individuals with phenylketonuria (PKU).Study design: We measured the levels of melatonin, a serotonin metabolite in the pinealocytes, in the blood and urine of individuals with PKU in a randomized double-blind placebo controlled crossover study consisting of three 3-week phases in 10 adults with PKU: phase 1 (washout), phase 2 (supplementation of large neutral amino acid [LNAA] tablets or placebo), and phase 3 (alternate supplementation). An overnight protocol to measure blood m...
Source: The Journal of Pediatrics - November 19, 2012 Category: Pediatrics Authors: Shoji Yano, Kathryn Moseley, Colleen Azen Tags: Original Articles Source Type: research

Chronic kidney disease in adolescent and adult patients with phenylketonuria
Conclusions In patients with PKU on a lifelong diet we could detect impaired renal function in 19 %, proteinuria in 31 %, and arterial hypertension in 23 %. Thus, chronic kidney disease may develop in PKU patients, and routine renal function tests should be performed during long-term follow-up. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s10545-012-9548-0Authors Julia B. Hennermann, Department of Pediatric Endocrinology, Gastroenterology and Metabolic Diseases, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, GermanySylvia Rolo...
Source: Journal of Inherited Metabolic Disease - November 8, 2012 Category: Internal Medicine Tags: Journal of Inherited Metabolic Disease Source Type: research

Children with phenylketonuria: basic audiological evaluation and suppression of otoacoustic emissions
CONCLUSION: The basic audiologic assessment do not identify hearing disorders in children with phenylketonuria; however, speech discrimination scores were lower and stapedial reflexes were higher in these children, which may indicate auditory processing disorders. The study of the suppression of transient otoacoustic emissions demonstrated integrity of the olivocochlear efferent system in children with phenylketonuria. (Source: Revista da Sociedade Brasileira de Fonoaudiologia)
Source: Revista da Sociedade Brasileira de Fonoaudiologia - September 29, 2012 Category: Audiology Source Type: research

BioMarin moves forward on drugs for amino acid disease PKU, dwarfism
BioMarin Pharmaceutical Inc. will take a mid-stage drug for the treatment of a rare phenylketonuria into Phase III testing. Novato-based BioMarin (NASDAQ: BMRN) said preliminary results from its four Phase II trials of pegylated recombinant phenylalanine ammonia lyase, or PEG-PAL, showed it was well tolerated and could prove efficacious. The Phase III program, generally the final stage of clinical trials before seeking Food and Drug Administration approval for a drug, will begin in second-quarter… (Source: bizjournals.com Health Care:Physician Practices headlines)
Source: bizjournals.com Health Care:Physician Practices headlines - September 26, 2012 Category: American Health Authors: Ron Leuty Source Type: research

BioMarin Announces Decision to Start Phase 3 Program for PEG-PAL in 2Q 2013
NOVATO, Calif., Sept. 26, 2012 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) announced today preliminary results from the Phase 2 program of PEG-PAL (PEGylated recombinant Phenylalanine Ammonia Lyase) for the treatment of phenylketonuria (PKU) demonstrating long-term retention, tolerability and providing evidence of efficacy. Based on these results, the company expects to start a pivotal Phase 3 study in the second quarter of 2013, following an anticipated end of Phase 2 meeting with the FDA in the first quarter of 2013. (Source: Medical News (via PRIMEZONE))
Source: Medical News (via PRIMEZONE) - September 26, 2012 Category: Pharmaceuticals Source Type: news

Refractory hypotension after bilateral nephrectomies in a Denys–Drash patient with phenylketonuria
Conclusions We discuss this case to offer a therapeutic option for the rare occurrence of persistent post-nephrectomy hypotension. Content Type Journal ArticleCategory Brief ReportPages 1-4DOI 10.1007/s00467-012-2311-9Authors Amanda B. Hassinger, Department of Pediatrics, Division of Critical Care Medicine, Women and Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222, USASudha Garimella, Department of Pediatrics, Division of Nephrology, Women and Children’s Hospital of Buffalo, Buffalo, NY, USA Journal Pediatric NephrologyOnline ISSN 1432-198XPrint ISSN 0931-041X (Source: Pediatric Nephrology)
Source: Pediatric Nephrology - September 19, 2012 Category: Urology & Nephrology Tags: Pediatric Nephrology Source Type: research

Maintaining trust in newborn screening: compliance and informed consent in the Netherlands.
Abstract Newborn screening consists of taking a few drops of blood from a baby's heel in the first week of life and testing it for a list of disorders. In the United States and most countries in Europe, newborn screening programs began in the 1960s and 1970s with screening for phenylketonuria (PKU), a rare metabolic disease that causes severe and irreversible mental retardation unless treated before problems arise. As knowledge about rare diseases expanded and new screening technologies were introduced-such as the tandem mass spectrometer and high-performance liquid chromatography-the same blood sample could be use...
Source: The Hastings Center Report - September 1, 2012 Category: Medical Ethics Authors: van der Burg S, Verweij M Tags: Hastings Cent Rep Source Type: research

Phenylketonuria, congenital hypothyroidism and haemoglobinopathies: public health issues for a Brazilian newborn screening program.
In this study, the frequency of detected congenital hypothyroidism, phenylketonuria and haemoglobinopathies in the State of Rio de Janeiro's (Brazil) Newborn Screening Program (NBSP) was analyzed between the years of 2005 and 2007. There were two Newborn Screening Reference Centers (named NSRC A and B) with programmatic differences. In 2007, overall detection coverage reached 80.7%. The increase in the incidence of congenital hypothyroidism (1:1,030 in 2007) was attributed to the reduction of neonatal TSH value limits over time. The incidence discrepancy of phenylketonuria between NSRC A (1:28,427) and B (1:16,522) might b...
Source: Cadernos de Saude Publica - September 1, 2012 Category: Global & Universal Authors: Botler J, Camacho LA, Cruz MM Tags: Cad Saude Publica Source Type: research

50 Years Ago in The Journal of Pediatrics: Comparison of Serum Phenylalanine Levels with Growth in Guthrie's Inhibition Assay in Newborn Infants
Scheel C, Berry HK. J Pediatr 1962;61:610-6 Scheel and Berry compare whole blood measurements of phenylalanine by using the bacterial inhibition assay developed by Guthrie with established procedures. They describe a 5% false-positive rate using the bacterial inhibition assay method and worry about the risk of false negatives, because the test depends on the infant's ingestion of sufficient protein. They conclude that “Guthrie's inhibition assay was probably not sensitive enough for use as a test for detection of phenylketonuria (PKU) in a nursery for newborn infants.” A year later, Guthrie would begin a pilot screeni...
Source: The Journal of Pediatrics - August 23, 2012 Category: Pediatrics Authors: Lainie Friedman Ross Tags: Original Articles Source Type: research

50 Years Ago in The Journal of Pediatrics: Identification of Heterozygotes with Phenylketonuria on Basis of Blood Tyrosine Responses
Anderson JA, Gravem H, Ertel R, Fisch R. J Pediatr 1962;61:603-9 Anderson et al report on a method to identify individuals heterozygous for phenylketonuria (PKU) by measuring serum tyrosine responses to oral l-phenylalanine loads. Using a 2-dose, 2-measurement methodology, the researchers were able to distinguish heterozygotes from noncarriers with only a 5% error. (Source: The Journal of Pediatrics)
Source: The Journal of Pediatrics - August 23, 2012 Category: Pediatrics Authors: Lainie Friedman Ross Tags: Original Articles Source Type: research

50 Years Ago in The Journal of Pediatrics: Mass Screening for Phenylketonuria
Wright SW. J Pediatr 1962;61:651-2 Despite the fact that Dr Robert Guthrie did not publish details of his methodology for screening infants for phenylketonuria until 1963, by 1962 the method had received wide publicity in the media, by parental organizations, and at scientific meetings. In this editorial, Wright notes that a pilot study of 400 000 infants was being planned using 2 methods to determine the sensitivity and specificity of Guthrie's bacterial inhibition assay test. Wright criticizes embarking on this mass testing program before information about the validity of the bacterial inhibition assay test is availa...
Source: The Journal of Pediatrics - August 23, 2012 Category: Pediatrics Authors: Lainie Friedman Ross Tags: Original Articles Source Type: research

Hepatocyte transplantation using the domino concept in a child with Tetrabiopterin non-responsive phenylketonuria.
Abstract Phenylketonuria is a metabolic disease caused by phenylalanine hydroxylase deficiency. Treatment is based on a strict natural protein-restricted diet that is associated with the risk of malnutrition and severe psychosocial burden. Oral administration of tetrahydrobiopterin can increase residual enzyme activity, but most patients with severe clinical phenotypes are non-responders. We performed liver cell transplantation in 6 years-old boy with severe tetrahydrobiopterin non-responsive phenylketonuria, who failed to comply with diet prescriptions. The transplanted hepatocytes were obtained in part from an ex...
Source: Cell Transplantation - August 10, 2012 Category: Cytology Authors: Stéphenne X, Debray FG, Smets F, Jazouli N, Sana G, Tondreau T, Menten R, Goffette P, Boemer F, Schoos R, Gersting SW, Najimi M, Muntau AC, Goyens P, Sokal EM Tags: Cell Transplant Source Type: research

[Neurological, neuropsychological, and ophtalmological evolution after one year of docosahexaenoic acid supplementation in phenylketonuric patients].
CONCLUSION. All the patients normalized the DHA levels after supplementation. Improvement in the P100 wave latencies, and fine motor skills was significant. No significant improvement in the other explorations was evident after supplementation. Further investigations seem advisable to establish a cause-effect relationship between DHA treatment and the slight improvement observed in some neurological functions. PMID: 22829083 [PubMed - in process] (Source: Revista de Neurologia)
Source: Revista de Neurologia - August 9, 2012 Category: Neurology Authors: Gutierrez-Mata AP, Vilaseca MA, Capdevila-Cirera A, Vidal-Oller M, Alonso-Colmenero I, Colome R, Lopez-Sala A, Lambruschini-Ferri N, Gutierrez A, Gassio R, Artuch R, Campistol J Tags: Rev Neurol Source Type: research

[Prenatal symptoms and diagnosis of inherited metabolic diseases.]
Abstract Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxi...
Source: Archives de Pediatrie - August 8, 2012 Category: Pediatrics Authors: Brassier A, Ottolenghi C, Boddaert N, Sonigo P, Attié-Bitach T, Millischer-Bellaiche AE, Baujat G, Cormier-Daire V, Valayannopoulos V, Seta N, Piraud M, Chadefaux-Vekemans B, Vianey-Saban C, Froissart R, de Lonlay P Tags: Arch Pediatr Source Type: research

Processing speed and executive abilities in children with phenylketonuria.
Conclusions: These findings indicate that information processing is slower and less efficient in children with PKU. In addition, processing speed and variability contribute to some, but not all, of the impairments in executive abilities observed in children with PKU. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (Source: Neuropsychology)
Source: Neuropsychology - August 6, 2012 Category: Neurology Authors: Janos, Alicia L.; Grange, Dorothy K.; Steiner, Robert D.; White, Desirée A. Source Type: research

Food Products Made with Glycomacropeptide, a Low-Phenylalanine Whey Protein, Provide a New Alternative to Amino Acid–Based Medical Foods for Nutrition Management of Phenylketonuria
Abstract: Phenylketonuria (PKU), an inborn error in phenylalanine metabolism, requires lifelong nutrition management with a low-phenylalanine diet, which includes a phenylalanine-free amino acid-based medical formula to provide the majority of an individual's protein needs. Compliance with this diet is often difficult for older children, adolescents, and adults with PKU. The whey protein glycomacropeptide (GMP) is ideally suited for the PKU diet because it is naturally low in phenylalanine. Nutritionally complete, acceptable medical foods and beverages can be made with GMP to increase the variety of protein sources for th...
Source: Journal of the American Dietetic Association - July 27, 2012 Category: Nutrition Authors: Sandra C. van Calcar, Denise M. Ney Tags: Review Source Type: research

Mutation spectrum of the PAH gene in the PKU patients from Khorasan Razavi province of Iran.
CONCLUSION: With this high detection rate of mutations in North-east of Iran, new strategy for carrier testing could be DNA sequencing of these four exons. The other exons and boundaries will be studied only when either one or no mutations are detected in the initial screen. PMID: 22763404 [PubMed - as supplied by publisher] (Source: Gene)
Source: Gene - July 2, 2012 Category: Genetics & Stem Cells Authors: Hamzehloei T, Hosseini SA, Vakili R, Mojarad M Tags: Gene Source Type: research

Single Amino Acid Forms Fibrils
Amyloid Disease: Phenylalanine aggregates may have a role in phenylketonuria (Source: Chemical and Engineering News)
Source: Chemical and Engineering News - June 25, 2012 Category: Chemistry Authors: Celia Henry Arnaud Source Type: research

Unexpectedly low asymmetric dimethylarginine (ADMA) and homocysteine levels in patients with phenylketonuria(PKU)
Content Type Journal ArticleCategory Letter to the EditorsPages 1-1DOI 10.1007/s10545-012-9502-1Authors Ömer Özcan, GATA Haydarpasa Training Hospital Department of Clinical Biochemistry, Uskudar, Istanbul, TurkeyOsman Metin Ipcioglu, GATA Haydarpasa Training Hospital Department of Clinical Biochemistry, Uskudar, Istanbul, TurkeyMustafa Gultepe, GATA Haydarpasa Training Hospital Department of Clinical Biochemistry, Uskudar, Istanbul, Turkey Journal Journal of Inherited Metabolic DiseaseOnline ISSN 1573-2665Print ISSN 0141-8955 (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 23, 2012 Category: Internal Medicine Tags: Journal of Inherited Metabolic Disease Source Type: research

An international survey of patients with tetrahydrobiopterin deficiencies presenting with hyperphenylalaninaemia
Conclusions BH4 deficiencies are a group of treatable pediatric neurotransmitter disorders that are characterized by motor dysfunction, mental retardation, impaired muscle tone, movement disorders and epileptic seizures. Although the outcomes of BH4 deficiencies are highly variable, early diagnosis and treatment result in improved outcomes. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s10545-012-9506-xAuthors Thomas Opladen, Division of Inborn Metabolic Diseases, University Childrens Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, GermanyGeorg F. Hoffmann...
Source: Journal of Inherited Metabolic Disease - June 23, 2012 Category: Internal Medicine Tags: Journal of Inherited Metabolic Disease Source Type: research

Informed Consent For Newborn Screening?
Parents must be considered when states decide to expand genetic screening programs for newborns, according to a new study that looked at mandatory testing panels and political pressure by advocacy groups. Nearly all infants in the United States undergo a heel prick within days of birth for a simple blood test to detect rare genetic disorders. For decades, state-based mandatory newborn screening programs have focused on disorders such as phenylketonuria (PKU) or hypothyroidism in which a prompt diagnosis and treatment could prevent disability or even death... (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - June 22, 2012 Category: Consumer Health News Tags: Pediatrics / Children's Health Source Type: news

Commentary: What degree of hyperphenylalaninaemia requires treatment?
Abstract Despite some 50 years’ experience in the treatment of phenylketonuria and numerous scientific publications on the subject there is no clear consensus as to what degree of hyperphenylalaninaemia will result in intellectual impairment. Studies of three main types, on untreated cases of moderate hyperphenylalaninaemia, on treated cases of phenylketonuria, and on the effects of current blood phenylalanine concentration on executive function, have lead to different conclusions. Overall, there appears to be a fairly strong case for limiting dietary treatment to individuals whose blood phenylalanine...
Source: Journal of Inherited Metabolic Disease - June 21, 2012 Category: Internal Medicine Tags: Journal of Inherited Metabolic Disease Source Type: research

Structural and Mechanistic Basis of the Interaction between a Pharmacological Chaperone and Human Phenylalanine Hydroxylase.
Abstract Not without a chaperone: Pharmacological chaperones are designed to bind and ideally stabilise their target protein. Here, we elucidate the molecular mechanism of a potential pharmacological chaperone to treat phenylketonuria. The crystal structure of human phenylalanine hydroxylase with compound IV may help in the rational design of more efficient compounds to treat this disease. PMID: 22549968 [PubMed - in process] (Source: Chembiochem)
Source: Chembiochem - June 18, 2012 Category: Biochemistry Authors: Torreblanca R, Lira-Navarrete E, Sancho J, Hurtado-Guerrero R Tags: Chembiochem Source Type: research

Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria
l & Ehud Gazit (Source: Nature Chemical Biology)
Source: Nature Chemical Biology - June 17, 2012 Category: Biology Authors: Lihi Adler-AbramovichLilach VaksOhad CarnyDorit TrudlerAndrea MagnoAmedeo CaflischDan FrenkelEhud Gazit Tags: Article Source Type: research

Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France
Conclusions: Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost-effective. The results of this analysis have been used to produce recommendations for the introduction of universal newborn screening for MCADD in France. (Source: BMC Pediatrics - Latest articles)
Source: BMC Pediatrics - Latest articles - June 8, 2012 Category: Pediatrics Authors: Francoise HamersCatherine Rumeau-Pichon Source Type: research