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Test Catalog

Test ID: GD65S    
Glutamic Acid Decarboxylase (GAD65) Antibody Assay, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Assessing susceptibility to autoimmune (type 1, insulin-dependent) diabetes mellitus and related endocrine disorders (eg, thyroiditis and pernicious anemia)

 

Distinguishing between patients with type 1 and type 2 diabetes

 

Confirming a diagnosis of stiff-man syndrome, autoimmune encephalitis, autoimmune ataxia, brain stem encephalitis, autoimmune epilepsy, autoimmune myelopathy; titers generally greater than or equal to 20.0 nmol/L

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Glutamic acid decarboxylase (GAD) is a neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). Antibodies directed against the 65-kD isoform of GAD (GAD65) are encountered at high titers (> or =20 nmol/L) in a variety of autoimmune neurologic disorders including stiff-person (Moersch-Woltman) syndrome, autoimmune cerebellitis, brain stem encephalitis, seizure disorders, and other myelopathies.

 

GAD65 antibody is also the major pancreatic islet antibody and an important serological marker of predisposition to type 1 diabetes. GAD65 autoantibody also serves as a marker of predisposition to other autoimmune disease that occur with type 1 diabetes, including thyroid disease (eg, thyrotoxicosis, Grave 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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

< or =0.02 nmol/L

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

High titers (> or =20.0 nmol/L) are found in classic stiff-person syndrome (93% positive) and in related autoimmune neurologic disorders (eg, acquired cerebellar ataxia, some acquired non-paraneoplastic encephalomyelopathies).

 

Diabetic patients with polyendocrine disorders also generally have glutamic acid decarboxylase (GAD65) antibody values 0.02 nmol/L or above.

 

Values in patients who have type 1 diabetes without a polyendocrine or autoimmune neurologic syndrome are usually 0.02 nmol/L or below. Low titers (0.03-19.9 nmol/L) are detectable in the serum of approximately 80% of type 1 diabetic patients. Conversely, low titers are detectable in the serum of less than 5% of patients with type 2 diabetes. Testing for autoimmune type 1 diabetes is complimented by testing for insulin, IA-2 and ZnT8 antibodies.

 

Eight percent of healthy Olmsted County residents over age 50 have low-positive values, and may be at risk for future autoimmune disease.

 

Values 0.03 nmol/L or above are consistent with susceptibility to autoimmune (type 1) diabetes and related endocrine disorders (thyroiditis and pernicious anemia).

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Antibodies specific for glutamic acid decarboxylase (GAD65) account for most, but not all, antibodies detected in the islet cell antibody test (IA-2). IA-2 (a protein tyrosine kinase-like protein) insulin and zinc transporter-8 antibodies are complementary islet cell antibodies.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. McKeon A, Tracy JA: GAD65 neurological autoimmunity. Muscle Nerve. 2017 Jul;56(1):15-27. doi: 10.1002/mus.25565.

2. Pittock SJ, Yoshikawa H, Ahlskog JE, et al: Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal and spinal cord dysfunction. Mayo Clin Proc. 2006;81:1207-1214

3. McKeon A, Robinson MT, McEvoy KM, et al: Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol. 2012 Feb;69(2):230-238

4. Steriade C, Britton J, Dale RC, et al: Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: Conceptual definitions. Epilepsia. 2020 Jul;61(7):1341-1351

5. Bingley PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab. 2010 Jan;95(1):25-33