Neurological disorders associated with glutamic acid decarboxylase antibodies: a Brazilian series Distúrbios neurológicos associadas a anticorpos anti-GAD (descarboxilase do ácido glutâmico): uma série de casos brasileira

Neurological disorders associated with glutamic acid decarboxylase (GAD) antibodies include stiff-person syndrome (SPS) and its variants — stiff trunk syndrome, stiff limbs syndrome, progressive encephalomyelitis with rigidity, SPS-plus and paraneoplastic SPS — as well as epilepsy and ataxia1-8. These syndromes are often found in association with other autoimmune disorders, such as diabetes mellitus, in more than one thirds of all cases, and, less commonly, those caused by antithyroid, antinuclear and antiparietal cell antibodies (5–10%)1-3,9-13. GAD is a cytoplasmic enzyme that accelerates the conversion of glutamic acid to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter present in the brain and spinal cord. GAD is synthesized mainly in presynaptic GABAergic neurons in the central nervous system and in the b cells in the islets of Langerhans in the pancreas. GAD autoantibodies are found in around 60 to 80% of SPS cases. Although there are two GAD isoforms 3⁄4 GAD65 and GAD67 3⁄4 the main target for GAD autoantibodies in SPS is GAD659-14. The pathogenetic role of autoantibodies in SPS is unclear. However, all SPS autoantigens identified to date are synaptic proteins involved in inhibitory synaptic transmission, such as GAD and amphiphysin (presynaptic antigens) and GABA(A) receptor-associated protein (GABARAP) and gephyrin (postsynaptic antigens). The autoantibodies anti-amphiphysin and anti-gephyrin have been linked to paraneoplastic SPS9-15. The objective of this study was to present the clinical and laboratory findings of 12 patients with neurological disorders associated with anti-GAD antibodies.