Determination of phenylalanine hydroxylase activity in patients with phenylketonuria and hyperphenylalaninemia.

The phenylalanine hydroxylase assay was modified by using biopterin, lysolecithin, and dithioerythritol. Liver tissue was obtained by percutaneous needle biopsies in patients with phenylketonuria (PKU) and hyperphenylalaninemia. The use of the naturally occurring cofactor biopterin is essential to measure low enzyme activities. Thirteen of 14 assay specimens in which no activity was detectable correlated with the clinical picture of classic PKU. Twelve assay specimens showed a residual activity up to 6% of normal. This group comprises patients with classic PKU and with so-called hyperphenylalaninemia. Four specimens ranged between 8.7 and 34.5% of the normal values. Patients in this group have developed normally so far without dietary treatment. It seems that patients with residual activity tolerate more phenylalanine in the diet than patients with no detectable activity. One infant with biochemical symptoms of classic PKU was found to have a normal phenylalanine hydroxylase activity.