Classical phenylketonuria is an autosomal recessive disease caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). The abolition of an invariant BamHI site located in the coding sequence of the PAH gene (exon 7) led to the recognition of two new point mutations at codon 272 and 273 (272gly----stop and 273ser----phe, respectively). Both mutations were detected in north eastern France...

Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Deficiency of the PAH enzyme causes classic phenylketonuria, a common genetic disorder. The human PAH gene has a TATA-less promoter with multiple transcriptional initiation sites. A 9-kilobase DNA fragment 5'-flanking to the human PAH gene is sufficient to confer tissue- and de...

The major cause of the different forms of hyperphenylalaninaemia (HPA) is mutations in the gene encoding phenylalanine hydroxylase (PAH). The aim of this study was to determine the mutations responsible for mild forms of HPA and to relate different clinical phenotypes of HPA patients to their PAH genotypes. Four "mild" mutations, including the most frequent A403V and R297H mutations, occurred e...

In the present study we report on the identification of ten novel mutations in the phenylalanine hydroxylase (PAH) gene of Brazilian patients with phenylketonuria (PKU): IVS5-54A>G, IVS6+17G>T, E205A, F240S, K274E, I318T, L321L, C357G, IVS11+17G>A and S411X. These mutations were detected during the characterization of the PAH genotypes of 115 patients with PKU from the southeast region of Brazi...

Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is a recently recognized variant of phenylketonuria, with a probable multifactorial molecular basis. In this study we have investigated the effect of BH4 on PAH gene expression in human hepatoma. Our results show that increased BH4 levels result in an enhancement of PAH activity and PAH protein, due to longer turnov...

Phenylketonuria (PKU) is an inborn error of amino acid metabolism with an autosomal recessive inheritance caused in most cases by mutations in the phenylalanine hydroxylase (PAH) gene. PKU has wide allelic heterogeneity. Here we report a novel heterozygous substitution (c.1223G>T (p.Arg408Leu)) in the PAH gene in an Iranian PKU family. The patient was 19-yr-old female with diagnosis of moderate...

Phenylketonuria (PKU; OMIM 261600) is one of the most common inborn errors of metabolism in Caucasians, with a frequency of 1 : 10 000 newborns in Europe. It is an autosomal recessive trait caused by a deficiency of hepatic phenylalanine hydroxylase (PAH; 1 phenylalanine 4-monooxygenase, EC 1.14.16.1), the main clinical signs of which are impaired cognitive development and function (Eisensmith ...

Phenylketonuria (PKU) is a metabolic disorder whereby phenylalanine metabolism deficient due to allelic variations in the gene for hydroxylase ( PAH ). There no cure PKU other than orthotopic liver transplantation, and standard of care patients limited dietary restrictions key amino acid supplementation. Therefore, Pah was edited pig fibroblasts generation clone piglets that harbor common sever...

The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Inherited mutations that result in PAH enzyme deficiency are the genetic cause of the autosomal recessive disorder phenylketonuria. Phe is the substrate for the PAH active site, but also an allosteric ligand that increases enzyme activity. Phe has been proposed to ...