Neurological abnormalities in phenylketonuria.

Abstract

Neurological disturbances were recorded in 46 out of 58 patients with phenylketonuria. An abnormal electroencephalogram was the most frequent finding. Motor signs were encountered in 31 cases. Only 2 patients showed true hyperkinesias and no other “extrapyramidal” signs were observed. Severe neurological dysfunction was most frequent in the most retarded patients. Severe motor signs only occurred in patients in their second and third decade. Twelve of the 58 patients were followed for 6 to 9 years. Five of these evolved supra-nuclear motor signs during the observation period. Two patients further showed definite progression of motor signs already present. The emergence or progression of motor disturbances always occurred in patients in their second or third decade. Thus, motor signs appear to be late phenomena while mental deficiency and epilepsy are early manifestations of phenylketonuria. This may indicate different pathogenetic mechanisms. It is suggested that motor signs are due to demyelination, previously demonstrated. The cause of demyelination may be a toxic effect of excess phenylalanine or its metabolites. Therefore, it should be reconsidered whether or not dietary treatment should be continued beyond the first decade.