Disease relevance of Phenylketonurias

• Phenylketonuria (PKU) is a metabolic disease caused by recessive mutations of the gene encoding the hepatic enzyme phenylalanine hydroxylase (PAH) [1].
• Vitamin B12 deficiency in adolescents and young adults with phenylketonuria [2].
• The Spr(-/-) mice exhibit phenylketonuria, dwarfism, and impaired body movement [3].
• Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria [4].
• Severe 6-pyruvoyl-tetrahydrobiopterin synthase deficiency is a tetrahydrobiopterin deficiency disorder that presents in infancy with developmental delay, seizures, and abnormal movements associated with hyperphenylalaninemia usually detectable by neonatal phenylketonuria screening programs [5].

Psychiatry related information on Phenylketonurias

• The "justification hypothesis" attributes mental retardation in phenylketonuria (PKU) to an inability of the heterozygous mother to deliver an appropriate amount of tyrosine to the PKU fetus who, in turn, is unable to correct for this deficiency because of its genetic constitution [6].
• The results of a postal questionnaire distributed to British members of Mensa failed to confirm an association of superior intelligence with torsion dystonia, retinoblastoma, or phenylketonuria, but were consistent with real associations between high IQ and infantile autism, gout, and myopia [7].
• Self-esteem of ten children with phenylketonuria was compared with that of seven unaffected siblings of children with PKU in a total of 11 families [8].
• It has been postulated that the significant incidence of learning disabilities in well-treated patients with phenylketonuria (PKU) may be due, in part, to reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membrane [9].
• Analysis of questionnaires, informal group meetings, and individual interviews with parents and their children with phenylketonuria gave insight on the attitudes and experiences surrounding discontinuance of the phenylalanine-restricted diet [10].

High impact information on Phenylketonurias

• Phenylketonuria is a metabolic disorder that results from a deficiency of the hepatic enzyme phenylalanine hydroxylase [11].
• We determined the effect on intellectual performance and behavior of the age at which dietary control was lost in 119 10-year-old children with phenylketonuria (PKU) who had started on a diet low in phenylalanine before the age of 65 days [12].
• Hyperphenylalaninemia due to a deficiency of biopterin. A variant form of phenylketonuria [13].
• Atypical phenylketonuria with normal dihydropteridine reductase activity [14].
• Phenylketonuria (PKU) is an autosomal recessive human genetic disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase, EC 1.14.16.1) [15].

Chemical compound and disease context of Phenylketonurias

• The data suggest that severe atypical or classic phenylketonuria (blood phenylalanine level, greater than 1100 mumol per liter) in the mother has a substantial cognitive effect on her offspring but that the effect of mild hyperphenylalaninemia may have been overstated in the past [16].
• Phenylketonuria: a new method for the simultaneous determination of plasma phenylalanine and tyrosine [17].
• Accumulation of a tetrahydroisoquinoline in phenylketonuria [18].
• Letter: Tetrahydrobiopterin treatment of variant form of phenylketonuria [19].
• Aspartame may imperil dietary control of phenylketonuria [20].

Biological context of Phenylketonurias

• Clinical phenylketonuria and mild hyperphenylalaninemia represent two different phenotypes of phenylalanine hydroxylase deficiency [21].
• Significant phenylalanine hydroxylation in vivo in patients with classical phenylketonuria [22].
• Characterization of phenylalanine hydroxylase alleles in untreated phenylketonuria patients from Victoria, Australia: origin of alleles and haplotypes [23].
• The maximum likelihood map presented permits confirmation that Scianna (SC) and a fourteenth locus, phenylketonuria (PKU), are on chromosome 1, although the location of the latter on the PGM1-AMY segment is uncertain [24].
• Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria [25].

Anatomical context of Phenylketonurias

• Phenylalanine has no effect on dihydropteridine reductase activity in phenylketonuria fibroblasts [26].
• Prenatal diagnosis of classic phenylketonuria (PKU) was performed in two at-risk families by means of a cloned human phenylalanine hydroxylase gene probe which was used to analyse DNA isolated from cultured amniotic fluid cells [27].
• Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients [28].
• The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria [29].
• No evidence for individual blood-brain barrier phenylalanine transport to influence clinical outcome in typical phenylketonuria patients [30].

Gene context of Phenylketonurias

• Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood [31].
• With regard to human disease, BH(4) deficiency due to autosomal recessive mutations in all enzymes (except sepiapterin reductase) have been described as a cause of hyperphenylalaninaemia [32].
• The hph-1 ENU-mutant mouse provides a model of tetrahydrobiopterin deficiency for studying hyperphenylalaninaemia, dopa-response dystonia, and vascular dysfunction [33].
• Phenylketonuria due to a deficiency of dihydropteridine reductase [34].
• We have studied the GTP-cyclohydrolase 1 (GCH-1) gene in 30 patients with the diagnosis of clinically definite (n = 20) or possible (n = 10) dopa-responsive dystonia (DRD) as well as in a child with atypical phenylketonuria due to complete GCH-1 deficiency [35].

Analytical, diagnostic and therapeutic context of Phenylketonurias

• Complete correction of hyperphenylalaninemia following liver-directed, recombinant AAV2/8 vector-mediated gene therapy in murine phenylketonuria [36].
• Biotinidase activity is assessed colorimetrically from dried samples of whole blood spotted on the same filter papers as used in the neonatal screening for phenylketonuria [37].
• The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed [38].
• A simple, rapid, and quantitative capillary zone electrophoresis method for phenylalanine analysis in serum has been developed, with the aim of providing an analytical tool, as an alternative to liquid and gas chromatography, for the routine laboratory diagnosis of phenylketonuria [39].
• We adapted the method of McCaman and Robins for fluorometry of phenylalanine to a microplate assay for routine phenylketonuria screening [40].

References