Primary and Secondary Neurotransmitter Defects


Chemical transmission is the major means of communication in the nervous system. Classical neurotransmitter systems involve inhibitory amino acids (GABA and glycine), excitatory amino acids (aspartate and glutamate), cholinergic transmission, biogenic amines (mainly adrenaline, noradrenaline, dopamine, and serotonin), purines and neuropeptides.

PRIMARY NEUROTRANSMITTER DISORDERS are a group of inherited neurometabolic diseases attributable to disturbances of neurotransmitter synthesis, degradation, or transport. Monoamine, GABA and glycine defects are the most common groups of human neurotransmitter diseases. The monoamines regulate brain functions such as movement, behavior, emotions, temperature, blood pressure and endocrine secretion. Disorders of monoamines include L-dopa related movement disorders and early complex encephalopathies. GABAergic transmission regulates epileptic mechanisms, cognition, behavior and arousal level. Clinical presentations include epileptic encephalopathies, intellectual disability, behavioral disturbances and episodes of lethargy. Glycine defects produce severe epileptic encephalopathy (due to defecst in the cleavage system) and hyperekplexia (due to mutations in glycine receptors or transporters). Other disorders include defects in the metabolism of pyridoxine and its derivative, pyridoxal phosphate, a cofactor necessary for the synthesis of several neurotransmitters.

Primary and secondary NT

Some neurotransmitter disorders are treatable and require the study of cerebrospinal fluid metabolites for diagnosis.

Primary neurotransmitter disorders include inborn errors of metabolism of dopamine, serotonin, GABA, glycine, pyridoxine and pyridoxal phosphate.

Detailed information about every defect can be found in the section: Neuropaediatric diseases and synapsis.

SECONDARY NEUROTRANSMITTER DISORDERS include a large and heterogeneous group of neurological diseases with abnormal neurotransmission that are not due to defects of synthesis, catabolism or transport but other different mechanisms. As examples mitochondrial disorders are very likely to show neurotransmitter defects due to energy mediated synaptic mechanisms; neurodegenerative disorders have reduced levels of neurotransmitters due to neuronal loss. Many other disorders and mechanisms can be included in this category of secondary neurotransmitter defects.