Brain Damage in the Aminoacidurias

A large number of genetic disorders of amino acid metabolism are coupled with neurologic symptoms, most commonly mental retardation. In many of these conditions, notably phenylketonuria and maple syrup disease, the enzyme implicated is normally absent from brain; neurologic symptoms are therefore produced indirectly, most likely the result of postnatal brain development taking place in an environment having a markedly distorted amino acid content. Excess tissue levels of a given amino acid may inhibit transport of other amino acids into the brain and their utilization for protein synthesis.(1–6) Cellular respiration,(7,8) synthesis of neurotransmitter substances(9–13) myelination,(14,15) and replication16 may also be affected. The possibility that under some circumstances amino acids may by themselves serve as neurotransmitters17 implies that deranged tissue levels may profoundly affect the function of the neuronal network.