Phenylketonuria (PKU) is an inborn error of amino acid metabolism. It occurs in approximately 1 in 10,000 of the United Kingdom population and follows an autosomal recessive pattern of inheritance. The disease results from a deficiency or defect of the enzyme phenylalanine hydroxylase which converts phenylalanine (phe) to tyrosine (tyr). In PKU there is an accumulation of phenylalanine that is toxic to the developing brain and causes mental retardation, spasticity and seizures. The treatment of PKU is the adherence to a special phe-restricted diet with amino acid, vitamin and mineral supplements. There are guidelines for the duration of dietary therapy in the United Kingdom produced by the Medical Research Council (MRC) Steering Committee on Phenylketonuria. These guidelines have been reviewed recently and lifelong diet is now recommended. This study began prior to the publication of these recommendations at a time when many centres discontinued diet in early adolescence. The rationale for stopping diet in adolescence is that the majority of brain development is complete by the end of childhood. The risks to the brain of the subsequent rise in phe levels in adolescence and adulthood after diet cessation remain unclear. The impetus to this study was the emergence of reports of adults with PKU (who had discontinued diet after childhood) developing new neurological signs such as spasticity of the limbs. Magnetic resonance imaging (MRI) of the brain in these patients showed an abnormal signal in the cerebral white matter and it was initially suggested that the MRI changes depicted the structural abnormalities causing the loss of function in these individuals. It was postulated by these authors that elevated phe levels in later life had a toxic effect on myelin and that adults with PKU were at risk of later onset neurological damage. This study was designed to obtain more information about brain function in adults with PKU who had stopped dietary treatment and to attempt to ascertain whether the MRI abnormalities described in several adults had any clinical significance
