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Unit Code 81596:
Glutamic Acid Decarboxylase (GAD65) Antibody Assay, Serum

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Useful For

Assessing susceptibility to autoimmune (type 1, insulin-dependent)

diabetes mellitus and related endocrine disorders (eg, thyroiditis and

pernicious anemia). Titers generally <20 nmol/L.

 

Distinguishing between patients with type 1 and type 2 diabetes.

Assays for gastric parietal cell, thyroglobulin, and thyroid peroxidase

antibodies, complement GAD65 antibody in this context. Titers

generally <20 nmol/L.

 

Confirming a diagnosis of stiff-man syndrome, autoimmune encephalitis,

cerebellitis, brain stem encephalitis, myelitis. Titers generally >20 nmol/L.

 

 

Confirming susceptibility to organ-specific neurological disorders

(eg, myasthenia gravis, Lambert-Eaton syndrome). Titers generally

<20 nmol/L.

Clinical Information

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 seen in a variety of autoimmune neurologic disorders

including stiff-man (Moersch-Woltman) syndrome, autoimmune

cerebellitis, brain stem encephalitis, seizure disorders, neuromyelitis

optica and other myelopathies, myasthenia gravis, Lambert-Eaton

syndrome, and dysautonomia.

 

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, Graves' disease, Hashimoto's

thyroiditis, hypothyroidism), pernicious anemia, premature ovarian

failure, Addison's disease, (idiopathic adrenocortical failure) and vitiligo.

Reference Values

< or = 0.02 nmol/L

Interpretation

High titers (> or = 20 nmol/L) are found in classic stiff-man syndrome

(93% positive) and in related autoimmune neurologic disorders

(eg, acquired cerebellar ataxia, some acquired nonparaneoplastic

encephalomyelopathies).

 

Diabetic patients with polyendocrine disorders also generally have

GAD65 antibody values > or = 20 nmol/L.

 

Values in patients who have type 1 diabetes without a polyendocrine

or autoimmune neurologic syndrome are usually <20 nmol/L. 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 <5% of type 2 diabetic patients.

 

Low titers are found in approximately 25% of patients with myasthenia

gravis, Lambert-Eaton syndrome, and rarer autoimmune neurological

disorders. Eight percent of healthy Olmsted County residents over age

50 have low positive values. These are not false positive; the antibodies

are inhibited by unlabelled GAD65 antigen and are accompanied in at

least 50% of cases by related organ-specific autoantibodies.

 

Values > or = 0.03 nmol/L are consistent with susceptibility to auto-

immune (type 1) diabetes and related endocrine disorders (thyroiditis

and pernicious anemia).

Cautions

Antibodies specific for GAD65 account for most, but not all, antibodies

detected in the islet cell antibody test. IA-2 (a protein tyrosine kinase-

like protein) and insulin antibodies are complimentary islet cell antibodies.

Special Instructions and Forms

• Paraneoplastic Evaluation Algorithm 

Clinical Reference

1.   Walikonis JE, Lennon VA:  Radioimmunoassay for glutamic acid

      decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man

      syndrome and a correlate of susceptibility to type 1 diabetes mellitus.

      Mayo Clin Proc 1998 December;73(12):1161-1166

 

2.   Kawasaki E, Yu L, Gianani R, et al:  Evaluation of islet cell

      antigen (ICA) 512/IA-2 autoantibody radioassays using overlapping

      ICA512/IA-2 constructs. J Clin Endocrinol Metab 1997

      February;82(2):375-380

 

3.   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

 

4.   Boylan KB, Lennon VA:  Cerebellar ataxia with glutamic acid

      decarboxylase antibody. Ann Neurol 1999;46:457 (abstract)

Key