We compared phenylketonuria (PKU) manifestations in two different gender siblings who were homozygous carriers of a rare phenylalanine hydroxylase (<i>PAH</i>) mutation, p.R155H, subjected to different treatments.
Phenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism.
Despite intensive study, there is no consensus on the atomistic details of the mechanism of O<sub>2</sub> binding and splitting by wild-type (WT) PAH and how it varies with PKU-inducing mutations, Arg158Gln and Glu280Lys.
Finally, comparison of the rat and human PAH structures show that hPAH is more dynamic, which is related to amino acid substitutions that enhance the flexibility of hPAH and may increase the susceptibility to PKU-associated mutations.
Bioinformatics software was used to predict the pathogenicity of novel variants and analyze the correlations between PAH gene variants and phenotypes of PKU patients.
Retrospective gene analysis of newborns with clinical phenylketonuria (PKU), identified compound heterozygote phenylalanine hydroxylase (PAH) gene mutations in eight of nine samples (89%).
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase that converts phe into tyrosine.
In this work, we study the functionality of seven yet uncharacterized PAH missense variants p.Asn167Tyr, p.Thr200Asn, p.Asp229Gly, p.Gly239Ala, p.Phe263Ser, p.Ala342Pro, and p.Ile406Met first identified in the Czech PKU/HPA patients.
Wide individual differences occurred in all groups, especially in patients with a classical PKU phenotype caused by <i>PAH</i> variants that fully abolish phenylalanine hydroxylase activity.
We compared the results of the phenotypic prediction based on APV and PAH activity respectively, and further explored the relationship between residual activity and phenotype in PKU patients.
Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment.
The established method of combing single-tube multiplex PCR with molecular hybridization technology can accurately and rapidly detect PAH gene mutations in Chinese and is suitable for screening of large PKU populations with clinical samples.
This study shows the nutritional and metabolic consequences of deviation from phenylalanine restriction and intake of PKU protein substitutes in nonadherent adult PKU patients.
In all cases, PAH variants were stabilized by the cofactor tetrahydrobiopterin (BH<sub>4</sub> ), a molecule known to alleviate symptoms in certain PKU patients.
In phenylketonuria (PKU), mutations of the phenylalanine hydroxylase (PAH) gene decrease the ability of PAH to convert phenylalanine (Phe) to tyrosine (Tyr), resulting in Phe accumulation in the blood and brain and disruption of neurotransmitter (NT) biosynthesis and metabolism.
A cohort of 2579 patients with PKU from Russia was analyzed for 25 common PAH gene mutations using custom allele-specific multiplex ligation-dependent probe amplification-based technology.