Termination of Strict Diet Therapy in Phenylketonuria*

Abstract

For several years and under various aspects diet termination in 22 early and late treated patients with phenylketonuria was studied. Time of diet termination was the completed 8th yr. For evaluation of possible functional CNS deficits, psychometric tests, methods for testing psychomotor behavior and neurophysiological parameters and registrations of sleep EEG were applied. EEG morphology was studied visually and the rhythms of the different phases of sleep were quantified by computerized spectral analysis. EEG was studied during diet therapy when phenylalanine levels in blood were low and after a relatively short period of 4 mo. with elevated phenylalanine blood levels. At least 2 yr after diet termination with correspondinly elevated phenylalanine blood levels the EEG was studied once more. Compared to the respective findings before diet termination in these patients there were no significant changes of the sleep EEG seen, neither on visual nor on spectral naalysis. Minor EEG changes in early treated children and overtly pathological EEG changes in late treated PKU patients with cerebral damage were seen both before and after diet termination. Ultrastructural CNS defects may be the cause of these anomalies which do not respond to the actual biochemical situation at the age of 8-10 yr. The morphology of such defects may include altered synaptic maturation and may occur already in an early phase before the diet therapy is implemented.