ABSTRACT
The existence of variant forms of hyperphenylalaninemia resulting from abnormalities of cofactor synthesis was predicted with the discovery of biopterin (Figure 21.1) and its role in the phenylalanine hydroxylase reaction [1-4]. The first patients were reported in the 1970s as an outgrowth of the programs of neonatal screening for PKU. A majority of the patients recognized early were diagnosed because they developed progressive cerebral deterioration despite an early neonatal diagnosis of hyperphenylalaninemia and effective dietary control of the levels of phenylalanine in blood.
