Phenylketonuria Research Today is a free monthly online journal that collates and summarizes the latest research about Phenylketonuria, including details on genetics, causes, symptoms, hereditary disorder.

Mutation analysis of phenylketonuria patients from Morocco: High prevalence of mutation G352fsdelG and detection of a novel mutation p.K85X.

Dahri S, Desviat LR, Pérez B, Leal F, Ugarte M, Chabraoui L

Service de Biochimie, Centre d'Etudes des Maladies Héréditaires du Métabolisme, Hôpital d'Enfants de Rabat et Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Moroccco.

OBJECTIVE:: The knowledge of the molecular basis of the Phenylketonuria (PKU, MIM# 261600) in different countries provides relevant information for undertaking specific and rational mutation detection strategies in each population and for the implementation of adequate dietary and cofactor treatment. There are no data available in Moroccan population. DESIGN AND METHODS:: In this work we describe the genetic analysis by mutation scanning using denaturing gradient gel electrophoresis (DGGE) and subsequent direct sequencing of 20 different PKU families from Morocco. We have also included the study of 7 Moroccan PKU patients living in Spain detected by the Spanish newborn screening program. RESULTS:: The mutational spectrum in the first sample included eight different changes, one of them, p.K85X, was novel. The most common mutation was the frame shift change p.G352fsdelG identified in 62.5% of the mutant chromosomes studied. Other changes (p.R176X, IVS10nt-11 g>a, p.W120X, p.A165T, p.R243X and p.R243Q) were identified, respectively, in 2 or 3 mutant alleles. All detected mutations were severe according to the classical phenotype of the patients. In the 7 patients living in Spain we have detected 4 severe mutations (p.G352fs, p.R176X, Y198fs and Exon3del) and also milder changes such as p.A403V, p.S196T, p.D145V and p.R408Q detected in 3 mild hyperphenylalaninemia (MHP) patients and a novel p.L258P found in a mild PKU patient. CONCLUSION:: The results provide important information on the distribution of PKU mutations in this Mediterranean area gaining insight into the genetic epidemiology of the disease.

Published 27 January 2010 in Clin Biochem, 43(1): 76-81.
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Articles on Phenylketonuria published 26 January 2010:

Effects of phenylalanine on the survival and neurite outgrowth of rat cortical neurons in primary cultures: possible involvement of brain-derived neurotrophic factor.   Mol Cell Biochem.

Phenylketonuria (PKU) is characterized by elevated levels of phenylalanine (Phe) in plasma and cerebrospinal fluid of PKU patients, leading to mental retardation. The developmental delay in the cerebral cortex is one of the characteristic pathologic changes in untreated phenylketonuria patients. This is thought to be due to the toxic effects of Phe and/or its metabolites; however, the underlying mechanisms are as yet unknown. In this study, using a model system in which cultured cortical ... [Abstract] [Full-text]

Articles on Phenylketonuria published 21 January 2010:

Study of inborn errors of metabolism in urine from patients with unexplained mental retardation.   J Inherit Metab Dis.

Mental retardation (MR) is a common disorder frequently of unknown origin. Because there are few studies regarding MR and inborn errors of metabolism (IEM), we aimed to identify patients with IEM from a cohort of 944 patients with unexplained MR. Biochemical examinations such as determination of creatine (Cr) metabolites, acylcarnitines, purine, and pyrimidines in urine were applied. We found seven patients with IEM [three with cerebral Cr deficiency syndromes (CCDS)], one with adenylosuccinate ... [Abstract] [Full-text]

Dietary interventions for phenylketonuria.   Cochrane Database Syst Rev.

BACKGROUND: Phenylketonuria is an inherited disease treated with dietary restriction of the amino acid phenylalanine. The diet is initiated in the neonatal period to prevent mental handicap; however, it is restrictive and can be difficult to follow. Whether the diet can be relaxed or discontinued during adolescence or should be continued for life remains a controversial issue, which we aim to address in this review. OBJECTIVES: To assess the effects of a low-phenylalanine diet commenced early ... [Abstract] [Full-text]

Articles on Phenylketonuria published 18 January 2010:

Variations in genotype-phenotype correlations in phenylketonuria patients.   Genet Mol Res, 9(1): 1-8.

Phenylalanine hydroxylase deficiency is a trait inherited in an autosomal recessive pattern; the associated phenotype varies considerably. This variation is mainly due to the considerable allelic heterogeneity in the phenylalanine hydroxylase enzyme locus. We examined the genotype-phenotype correlation in 54 phenylketonuria (PKU) patients from Minas Gerais, Brazil. Two systems were used. The first was a phenotype prediction system based on arbitrary values (AV) attributed to each mutation and ... [Abstract] [Full-text]

Articles on Phenylketonuria published 11 January 2010:

Tetrahydrobiopterin responsiveness after extended loading test of 12 Danish PKU patients with the Y414C mutation.   J Inherit Metab Dis.

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phe accumulation can lead to cognitive impairment. Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations. We tested 12 patients with PKU, 8-29 years of age, all carrying the common Y414C mutation in the PAH gene. Three were homozygous and ... [Abstract] [Full-text]

Articles on Phenylketonuria published 16 December 2009:

Converting an injectable protein therapeutic into an oral form: phenylalanine ammonia lyase for phenylketonuria.   Mol Genet Metab, 99(1): 4-9.

Phenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; ... [Abstract] [Full-text]

Extended use and long-term storage of newborn screening blood spots in Japan.   Pediatr Int.

Abstract Background: Residual dried blood spots (DBS) remaining after routine newborn screening (NBS) tests are candidate specimens for extended uses such as quality assurance and the development of new technology. A trial of NBS by tandem mass-spectrometry was launched in 2004 in Japan. We designed the present research to analyze the attitudes of the public, patients' families, and medical professionals toward the extended use and long-term storage of residual DBS, and to construct a ... [Abstract] [Full-text]

Articles on Phenylketonuria published 9 December 2009:

Evaluation of somatic development in adult patients with previously undiagnosed and/or untreated phenylketonuria.   Med Princ Pract, 19(1): 46-50.

OBJECTIVE: To evaluate physical growth, development and nutritional status in adults with previously undiagnosed/ untreated phenylketonuria (PKU). METHODS: Four hundred adults (201 females and 199 males) with severe intellectual disability who were born prior to compulsory neonatal screening (before 1976) and who resided in social welfare homes in southeastern Poland were screened for PKU. The screening was performed by blood test using a tandem mass spectrometry method (MS/MS) and was ... [Abstract] [Full-text]

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