Neurological aspects of adult phenylketonuria

Phenylketonuria, an autosomal recessively transmitted disorder of amino acid metabolism, is caused by a deficiency of hepatic phenylalanine hydroxylase converting phenylalanine to tyrosine. Thus, phenylalanine accumulates to plasma levels exceeding 1200 mumol/l. Untreated phenylketonuria is characterized by microcephaly, epilepsy, severe mental retardation and, in some cases, progressive supranuclear motor disturbances. These symptoms can largely be prevented by the early start of a phenylalanine-restricted diet. Neurological investigations of treated patients reveal only minor neurological signs, such as tremor or brisk deep tendon reflexes. Magnetic resonance imaging shows white matter abnormalities. However, in single patients, progressive neurological symptoms occurred. Thus, the long-term prognosis of treated phenylketonuria is still under discussion.