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.
Category
Inherited metabolic disorder
Brite
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Metabolic disorders
Inborn errors of metabolism
5C50 Inborn errors of amino acid or other organic acid metabolism
H00167 Phenylketonuria
Pathway-based classification of diseases [BR:br08402]
Amino acid metabolism
nt06016 Phenylalanine and tyrosine metabolism
H00167 Phenylketonuria
Thony B, Leimbacher W, Blau N, Harvie A, Heizmann CW
Title
Hyperphenylalaninemia due to defects in tetrahydrobiopterin metabolism: molecular characterization of mutations in 6-pyruvoyl-tetrahydropterin synthase.