Untreated PKU is associated with an abnormal phenotype including growth failure, microcephaly, seizures and intellectual impairment. The pathogenesis of these abnormalities involves the neurotoxic effects of hyperphenylalaninaemia, which are linked to Tyr deficiency (leading to a decrease in catecholamine neurotransmitters), the effect of elevated Phe concentrations on transport of other aminoacids across the blood brain barrier, accumulation of toxic by-products of Phe metabolism. Magnetic resonance imaging (MRI) has revealed white matter lesions in the brain of adult PKU patients, including hypomyelination and demyelination.