Treatable neurotransmitter deficiency in mild phenylketonuria

The authors describe a case of neurologic involvement in mild hyperphenylal aninemia (HPA), not due to tetrahydrobiopterin (BH4) deficiency, with low l evels of monoamine neurotransmitter metabolites in CSF. The combined BH4-Ph e loading test suggested a BH4 response, confirmed by clinical improvement after BH4 therapy. Molecular study revealed a compound heterozygosity of th e phenylalanine hydroxylase alleles: a mild HPA-associated mutation (T380M) and the new mutation D151E. This case demonstrates that even mild HPA, gen erally considered a benign disorder, may present neurologic impairment.