Long term studies of untreated phenylketonuria II: the plasma phenylalanine level

The plasma phenylalanine level was measured on at least two occasions, usually more, in 81 patients with phenylketonuria on unrestricted diets. The distribution of the individual levels was gaussian and the mean (31 mg/100 ml) did not change significantly over an average span of 12.7 years. Persistent individual differences were found but so were unexpected and inexplicable high or low plasma phenylalanine levels in particular patients. Variations in dietary phenylalanine intake did not explain the differences in plasma phenylalanine levels between individuals. There was no clear relationship between the degree of mental disability and the average plasma phenylalanine except that those with the least brain damage had slightly lower average levels (24.2 mg/100 ml). The difficulties of demonstrating genetic heterogeneity in phenylketonuria are illustrated even though this is likely present. It is argued that the assumption of a direct quantitative relationship between the degree of brain damage and the height of the plasma phenylalanine level is an oversimplification.