Cerebrospinal fluid analysis in the diagnosis of treatable inherited disorders of neurotransmitter metabolism

Abstract

The inherited disorders affecting dopamine and serotonin (5-hydroxytryptamine) metabolism are being recognized as treatable causes of neurological problems that affect infants, children and adults. Diagnosis of these conditions in many cases requires that neurotransmitter metabolites, and the cofactors required for their synthesis, be measured in cerebrospinal fluid (CSF). This review will concentrate on the inherited disorders that affect dopamine and serotonin biosynthesis and an overview will be given of the metabolism of these two neurotransmitters. The metabolite pattern found in each known defect is also given. Emphasis is put on the need to collect and handle CSF in the appropriate manner if meaningful results from neurotransmitter metabolite measurements are to be obtained. The clinical phenotypes that might be associated with neurotransmitter deficiency are described, and finally, speculation will be provided as to the metabolite patterns that might occur in the CSF in disorders that are yet to be discovered.