Diagnosis of phenylalanine hydroxylase deficiency (phenylketonuria)

Needle liver biopsies were carried out on patients with phenylketonuria (PKU) to establish a diagnosis either of partial or complete phenylalanine hydroxylase (PH) deficiency. Ten phenylketonuric patients and two parents were studied. Nine of the ten patients had completed a three-day oral phenylalanine challenge. Each met the accepted criteria as having classic PKU, based on a sustained rise in the serum phenylalanine level greater than 20 mg/dL. A diagnosis of classic PKU was confirmed in six patients by the absence of hepatic PH activity. Four of the PKU patients had PH activity ranging from 9% to 24% of that found in liver from non-PKU control subjects. The two parents had 27% and 42% of the PH activity found in the control subjects; their child had no activity. Current methods for distinguishing partial from complete PH deficiency are not always reliable, and the degree of the deficiency can best be established by direct measurement of the enzyme in liver.