Phenylketonuria;
Hyperphenylalaninemia, BH4-deficient

Phenylketonuria (PKU) is one of the most common inborn errors of metabolism marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH), leading to a toxic accumulation of phenylalanine in the blood and multiple tissues and potentially to intellectual disability, delayed speech, seizures, and behavior abnormalities. Deficiency of tetrahydrobiopterin (BH4), the cofactor of PAH, is caused by defects of the enzymes in pterin biosynthesis. Because BH4 is also a cofactor of tyrosine hydroxylase and tryptophan hydroxylase in neurotransmitter synthesis, BH4-deficient hyperphenylalaninemia is characterized by neurotransmitter deficiencies.

Inherited metabolic disease; Nervous system disease

nt06016  Phenylalanine and tyrosine metabolism

PAH; phenylalanine hydroxylase [HSA:5053] [KO:K00500]
(BH4-deficient, A) QDPR; quinoid dihydropteridine reductase [HSA:5860] [KO:K00357]
(BH4-deficient, B) GCH1; GTP cyclohydrolase 1 [HSA:2643] [KO:K01495]
(BH4-deficient, C) PTS; 6-pyruvoyltetrahydropterin synthase [HSA:5805] [KO:K01737]
(BH4-deficient, D) PCBD1; pterin-4 alpha-carbinolamine dehydratase [HSA:5092] [KO:K01724]

Pegvaliase [DR:D11077]
Sapropterin dihydrochloride [DR:D01798]

PMID:23430527

Lindegren ML, Krishnaswami S, Reimschisel T, Fonnesbeck C, Sathe NA, McPheeters ML

A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria.

JIMD Rep 8:109-19 (2013)
DOI:10.1007/8904_2012_168