Presentation, diagnosis, and treatment of the disorders of monoamine neurotransmitter metabolism.

For many years, all of the described cases of monoamine neurotransmitter deficiency were associated with hyperphenylalaninemia that was generally detected at neonatal screening. It is now clear that inherited deficiency of monoamines often occurs in the absence of hyperphenylalaninemia and that the normal battery of screening tests used to investigate individuals with suspected metabolic disease will not detect these cases. Diagnosis in this situation must rely heavily on clinical suspicion. This article, therefore, describes the presentation and clinical symptoms that result from defective monoamine neurotransmission; outlines therapeutic approaches; and explains how cerebrospinal fluid profiles of monoamine metabolites, their precursors, and the cofactor required for monoamine synthesis can be used to pinpoint the exact site of the metabolic lesion.