Disorders of neurotransmission

Abstract

Monogenic defects of neurotransmission have become recognized as a cause of early onset, severe, progressive encephalopathies. The diagnosis is mostly based on the quantitative determination of the neurotransmitters or their metabolites in cerebrospinal fluid (CSF), i. e., the amino acids glutamate, glycine, and γ-aminobutyric acid (GABA), the acidic metabolites of the biogenic monoamines, and individual pterin species (Hoffmann et al. 1998). In contrast to inborn errors in catabolic pathways, neurotransmitter defects are reflected by the interplay of biosynthesis, degradation, and receptor status. Even borderline abnormalities can be diagnostic, but their recognition requires a strictly standardized sampling protocol and adequate age-related reference values. All laboratories have their own reference values that differ because of local variations in the technique of CSF sampling and the precise aliquot used for analysis. Because of these special logistics of sampling and transport, as well as demanding laboratory techniques due to very low metabolite concentrations, "neurotransmitter defects" are investigated in few specialized laboratories worldwide, and consequently only a small number of patients has been diagnosed. Therefore we suspect a substantial underdiagnosis.