Monoamine neurotransmitters and movement disorders in children and adults

Abstract

Neurotransmitter disorders comprise a rapidly expanding phenotypically and genetically heterogeneous group. Most of these disorders start in infancy through to childhood, although some forms may arise in adolescence and adulthood, and have various presentations. They may be overlooked if the phenotype leads to misdiagnoses involving various combinations of developmental disorders, hypotonia and movement disorders (dystonia, hyperkinesia, parkinsonism) or other clinical manifestations, such as sleep alterations and mood disorders. Neurotransmitter metabolite levels in cerebrospinal fluid (CSF) may help us to analyze and better understand the metabolic cascade and changes in dopamine and serotonin synthesis, and also guide genetic testing. Indeed, it is important to recognize these disorders in their early stages as they can be greatly improved by drug treatments, and if clinical responses are insufficient, then other agents that may enhance neurotransmission, such as serotonergic drugs and tetrahydrobiopterin (BH4) supplementation, could be considered. Also, a precise genetic diagnosis should be established by gene panels for dystonia, SNP microarrays and whole-exome sequencing. The present brief survey aims to review the present state of the art for the most commonly described and rare disorders of dopamine and serotonin, as well as cofactor deficiencies and dysfunctions, with an overview of clinical features, diagnostic strategies and treatments. Moreover, although these are mainly disorders of infants and children, many may nevertheless reach adulthood; thus, their evolution and treatments should be well known not only by pediatricians, but by neurologists as well, as the latter may be in charge at the stage of diagnosis (rarely) and during the follow-up of these rare patients.

Keywords: CSF neurotransmitters; Children; Dopa-responsive dystonia; Dopamine; Dystonia; Monoamine neurotransmitter disorders; Movement disorders; Parkinsonism; Serotonin; Tetrahydrobiopterin defects; Therapeutics.