Treatable neurotransmitter deficiency in mild phenylketonuria

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