A comparative exploration of monoamine neurotransmitter transport disorders: mechanisms, clinical manifestations, and therapeutic approaches

Abstract

Neurotransmitters play important roles in brain function, influencing cognition, movement, and behavior. Disruption in neurotransmitter biosynthesis, expression, transport, or function due to genetic mutations can lead to various neurological and psychiatric disorders with variable age of onset. Catecholamines like dopamine, norepinephrine, epinephrine, and serotonin are key monoamines transported by specific transporters, including the dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2). Disorders that involve monoamine neurotransmitter transport include dopamine transporter deficiency syndrome (DTDS) and brain dopamine-serotonin vesicular disorders (PKDYS2). These rare syndromes manifest with movement disorders and neuropsychiatric symptoms. DTDS results from a mutation in the SLC6A3 gene affecting dopamine reuptake, while PKDYS2 involves a mutation in the SLC18A2 gene impairing the transport of dopamine and serotonin. This review provides a comparative analysis of the diagnostic approaches, the management strategies, and the outcomes for these distinct disorders.

Keywords: 5-HIAA, 5-Hydroxyindoleacetic Acid; AADC, Aromatic L-Amino Acid Decarboxylase; CSF, Cerebrospinal Fluid; DA, Dopamine; DAT, Dopamine Transporter; DTDS; DTDS, Dopamine Transporter Deficiency Syndrome; EEG, Electroencephalography; ENMG, Electroneuromyography and Nerve Conduction Studies; GAT-1, Gamma-Aminobutyric Acid (GABA) Transporter 1; HVA, Homovanillic Acid; MAO-A, Monoamine Oxidase A; MAO-B, Monoamine Oxidase B; NE, Norepinephrine; PKDYS1, Infantile-Onset Parkinsonism Dystonia 1; PKDYS2; PKDYS2, Infantile-Onset Parkinsonism Dystonia 2; SNP, Single Nucleotide Polymorphism; VMAT2, Vesicular Monoamine Transporter 2; WES, Whole Exome Sequencing; dopamine transporter; monoamine neurotransmitter transporters.

Figure 1

Overview of normal neurotransmission of dopamine and serotonin

Figure 2

Monoamine neurotransmitter disorders