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  • Title: Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus, and polyendocrine autoimmunity.
    Author: Saiz A, Arpa J, Sagasta A, Casamitjana R, Zarranz JJ, Tolosa E, Graus F.
    Journal: Neurology; 1997 Oct; 49(4):1026-30. PubMed ID: 9339684.
    Abstract:
    BACKGROUND: Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in stiff-man syndrome (SMS) and insulin-dependent diabetes mellitus (IDDM). GAD autoantibodies (GAD-Abs) are reported in a few patients with cerebellar ataxia, but their relevance is unclear. We describe three patients with cerebellar ataxia and GAD-Abs. METHODS: GAD-Abs were assayed by radioimmunoassay (RIA) and immunohistochemistry and confirmed by immunoblot of recombinant human GAD65. The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects. RESULTS: The three patients with ataxia and GAD-Abs were women (mean age, 63 years) with an isolated progressive cerebellar disorder, family history of IDDM, late-onset IDDM, and several positive serum organ-specific autoantibodies. Two patients had autoimmune thyroiditis, and one had pernicious anemia. CSF analysis demonstrated oligoclonal IgG bands and intrathecal synthesis of GAD-Abs. By RIA, GAD-Ab titers from the three patients were similar to those of SMS and significantly higher, without overlap, than the titers of IDDM patients. GAD-Abs were absent in the 64 patients with cerebellar ataxia and no evidence of autoimmune disorders. CONCLUSIONS: These findings suggest a link of GAD autoimmunity not only with SMS but also with cerebellar dysfunction. GAD-Abs should be sought in patients with cerebellar ataxia who have late-onset IDDM and other organ-specific autoimmune manifestations.
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