Two general types of disorder have been described. In one there is defective activity of dihydropteridine reductase, and in the other the defect is in biopterin cofactor synthesis. The clinical manifestations appear to be the same. Most patients have been recognized because of the presence of progressive cerebral disease despite excellent control of the plasma levels of phenylalanine. Tetrahydrobiopterin is also the cofactor for the hydroxylation of the tryptophan and tyrosine.
Involved patients are markedly hypotonic and spastic.
They display dystonic posturing. Mental retardation is profound, and drooling is a prominent feature. Seizures, including myoclonic seizures, are seen, and the EEG may be abnormal. The diagnosis of these disorders can be made in a number of ways. The simplest is the administration of tetrahydrobiopterin.