tetrahydrobiopterin deficiency

any of several disorders in the synthesis or regeneration of the cofactor tetrahydrobiopterin; clinical presentation is usually similar to phenylketonuria but because the cofactor also functions in the synthesis of various monoamine neurotransmitters, the disorders are not responsive to dietary phenylalanine restriction unless the missing neurotransmitters can also be supplied. Causes include mutations in the genes encoding 6,7-dihydropteridine reductase, GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase, and pterin 4-α-carbinolamine dehydratase. There are also several variant forms not presenting with hyperphenylalaninemia, including dopa-responsive dystonia due to defects in GTP cyclohydrolase I and in sepiapterin reductase.