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. The patient with PKU will have no change in the level of phenylalanine following administration of the cofactor. A few patients with reductase defects have been missed using the BH 4 loading test, but Danks has pointed out that his recommendation was for parenteral administration of BH 4 and the failures have been with the oral use of the compound.