Neurotransmitter defects and treatment of disorders of hyperphenylalaninemia

The disordered biosynthesis of dopamine, norepinephrine, and serotonin in brain in untreated PKU is corrected by dietary restriction of phenylalanine. Low levels of biogenic amine metabolites were measured in cerebrospinal fluid from three patients with classical PKU; metabolite concentrations increased after dietary treatment. In a variant of hyperphenylalaninemia caused by deficiency of dihydropteridine reductase, there is defective metabolism of biogenic amines despite dietary restriction of phenylalanine. Two siblings with DHPR deficiency had low amine metabolite values in CSF; in one patient the metabolic defect was corrected by administration of hydroxylated amino acid precursors. Defective biosynthesis of biogenic amines in brain in disorders associated with hyperphenylalaninemia and evaluation of specific dietary treatments can be determined by analysis of neurotransmitter metabolites in CSF.