Interpretive Handbook

Test 84221 :
Glutamic Acid Decarboxylase (GAD65) Antibody Assay, Spinal Fluid


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's thyroiditis, hypothyroidism), pernicious anemia, premature ovarian failure, Addison's 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.


Possible use in evaluating patients with stiff-man syndrome, autoimmune cerebellitis and other acquired central nervous system disorders affecting gabaminergic neurotransmission. Clinical utility remains to be determined.

Interpretation Provides information to assist in interpretation of the test results

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.




< or =0.02 nmol/L



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