Neuropsychological Functioning in Early-Treated Phenylketonuria – A Review

Abstract

Phenylketonuria (PKU) is an inborn error of metabolism involving a deficiency of the enzyme phenylalanine hydroxylase. This condition results in elevated levels of phenylalanine and low levels of tyrosine. If left untreated, severe neuropathology and neurobehavioral sequelae manifest. The implementation of newborn screening and early dietary treatment has significantly reduced such morbidity. Despite relatively preserved general intellectual functioning, in early-treated PKU individuals subtle cognitive and behavioral deficits are still apparent. This paper provides a review of the evidence for impairment in information processing, executive function, memory and learning, academic achievement and behavior. This paper also reviews the two primary theories proposed to date relating to the underlying mechanisms for the cognitive and behavioral deficits encountered in treated PKU patients, namely prefrontal dysfunction and white matter abnormalities. Although more research is required, the literature to date suggests that early-treated PKU individuals are at risk of subtle neurobehavioral deficits across a range of neuropsychological domains. Thus, PKU patients should be closely monitored so that problems are detected early and appropriate interventions are put in place to ensure that individuals reach their full potential.