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Possible use in evaluating patients with stiff-man syndrome, autoimmune cerebellitis and other acquired central nervous system disorders affecting gabaminergic neurotransmission
Glutamic acid decarboxylase (GAD) is a neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). Serum antibodies directed against the 65-kd isoform of GAD (GAD65) are detected in heightened frequency in a variety of autoimmune neurologic disorders, including stiff-man (Moersch-Woltman) syndrome, autoimmune cerebellitis, some idiopathically acquired epilepsies, some rare acquired encephalomyelopathies with and without neoplasia, and in myasthenia gravis and Lambert-Eaton myasthenic syndrome.
GAD65 antibodies account for the majority of clinically recognized pancreatic islet cell antibodies, and are an important serological marker of predisposition to type 1 (insulin-dependent) diabetes. GAD65 autoantibodies also serve as a marker of predisposition to autoimmune disorders that commonly or sometimes coexist with type 1 diabetes, including autoimmune thyroid disease (eg, thyrotoxicosis, Graves disease, Hashimoto thyroiditis, hypothyroidism), pernicious anemia, premature ovarian failure, Addison disease (idiopathic adrenocortical failure), and vitiligo. GAD65 antibodies are found in the serum of approximately 8% of healthy subjects older than age 50, usually in low titer, but often accompanied by related "thyrogastric" autoantibodies.
< or =0.02 nmol/L
Intrathecal synthesis of GAD65 antibody has been demonstrated in patients with stiff-man syndrome, but cerebrospinal fluid (CSF) values are log orders lower than serum. We have not determined the frequency of GAD65 antibodies in CSF of patients with various diagnoses.
Clinical utility of this test remains to be determined.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held one week and assayed if sufficiently decayed, or canceled if radioactivity remains.
1. Saiz A, Arpa J, Sagasta A, et al: Autoantibodies to glutamic acid decarboxylase in three patients with cerebellar ataxia, late-onset insulin-dependent diabetes mellitus and polyendocrine autoimmunity. Neurology 1997 October;49(4):1026-1030
2. Boylan KB, Lennon VA: Cerebellar ataxia with glutamic acid decarboxylase antibody. Ann Neurol 1999;46:457 (abstract)
3. Dalakas MC, Li M, Fujii M, Jacobowitz DM: Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies. Neurology 2001 September 11;57:780-784