Treatment factors and neuropsychological outcome in phenylketonuria

Abstract

Phenylketonuria (PKU) is an inherited metabolic disease that affects about one in 10,000 of the population worldwide. In the classical form of the condition, the hepatic enzyme phenylalanine hydroxlase is absent or much reduced. If untreated, severe or profound mental handicap customarily results due to the accumulation of dietary phenylalanine (phe) which is neurotoxic. The mechanism by which phe impairs growth in the immature nervous system is little understood, but myelin metabolism appears to be disturbed. Treatment is by reduction of phe in daily food intake. Treatment should ideally begin in the neonatal period if intellectual loss is to be avoided. However, the safe range of phe concentrations during treatment and the age at which treatment can be discontinued without further damage being inflicted are uncertain. The studies reported in this volume investigated neuropsychological outcomes of treatment control and cessation factors. In addition, the question of whether executive functions are especially vulnerable to elevated phe concentrations during treatment was addressed. Patient samples conformed to the practice adopted in the West of Scotland regional centre for the management of PKU of maintaining dietary treatment until age 10 or beyond. Almost exclusively, negative findings emerged. These suggested that, if control of phe intake conforms to current UK recommendations for the preschool and primary years, neither global nor specific intellectual deficit result. Furthermore, the data supported the view that cessation of treatment at 10 years of age does not have harmful consequences. These findings have direct implications for the formulation of clinical policy on the treatment of PKU, but it must be recognized that the history of the successful treatment of PKU and mass screening for the disease spans a mere three decades. Thus, treatment outcome research to date is based only on children and young adults. In future investigations, a life-span approach will be required before the issues raised in this thesis can be finally settled.