. (1976). Archives of Disease in Childhood, 51, 771. Biopterin derivatives in normal and phenylketonuric patients after oral loads of L-phenylalanine, L-tyrosine, and L-tryptophan. Plasma biopterin derivatives studied in 10 normal and 21 phenylketonuric children showed a significantly high concentration in the latter group. Biopterin derivatives correlated with plasma phenylalanine concentration, but in normal adults given an oral phenylalanine load the rate of increase with phenylalanine differed from that in phenylketonuric patients.A patient with hyperphenylalaninaemia, not due to phenylketonuria, had an abnormal biopterin derivatives response to phenylalanine distinct from that of patients with classical phenylketonuria. This may be a useful investigation to differentiate some variants of phenylketonuria.Patients with hyperphenylalaninaemia do not necessarily have phenylketonuria, due to an almost total deficiency of the hepatic enzyme phenylalanine hydroxylase, and diagnosis is complicated by the several variants or atypical forms of phenylketonuria. These variants are currently identified by criteria including plasma phenylalanine concentrations lower than those found in classical phenylketonuria; an increased tolerance to administered phenylalanine over a few hours; and the ability of a patient to sustain a diet containing about 250-500 mg phenylalanine per day rather than 150-250 mg/day in classical phenylketonuria.