Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia

Guanosine 5'-triphosphate cyclohydrolase I (GCH) mutants (H144P and T186K) associated with dominant dopa-responsive dystonia were enzymatically inactive and inhibited the normal enzyme, suggesting that GCH activity in a heterozygote was <50% of control. The M211I mutant associated with recessive hyperphenylalaninemia was slightly active and had no inhibitory effects, so GCH activity in a heterozygote would be <50% of normal; therefore hyperphenylalaninemia would be evident only in homozygotes.