[Possible explanation of the high degree of IQ variability in subjects with classical phenylketonuria]

Descriptions of cases of PKU presenting the plain metabolic defect but little or no brain damage are becoming more and more frequent. The author admits the existence of a genetic enzyme system independent of the PKU gene (X). It is probably acting in the brain cells, restoring more or less normal aminoacid balance at this level. Full enzymatic activity and optimal protection against the deleterious effect of phenylalanine would result from the homogenous gene (XX), somewhat lower activity from the heterozygous gene (Xx). Homozygous xx-individuals would lack the protecting enzyme and therefore be highly exposed to damage by phenylalanine. Hydroxylation of phenylalanine in brain tissue has been reported for several animal species by a series of authors who incriminate either a brain isoenzyme of phenylalanine hydroxylase or tyrosine hydroxylase. The main aim of this paper is to suggest search for such types of enzyme in human brain cells to all the workers having access to human brain tissue.