Glutamic acid decarboxylase antibodies (GAD-Abs) have been identified in neurologic (ie. Stiff Person Syndrome) and non-neurologic (ie. Type I diabetes) autoimmune conditions. Published reports and small case series have identified a subset of GAD antibody positive patients with autonomic symptoms including gastrointestinal dysmotility and autonomic neuropathy. While GABAergic neurons exist within the autonomic and enteric nervous systems the pathophysiologic role of GAD-Abs as either directly pathogenic versus a marker of neuronal injury remains controversial.  Additionally, the autonomic complications associated with GAD-Abs are still being defined as is the role of immunomodulatory therapies.

Retrospective chart review was utilized to identify the cohort. Detailed demographic data, clinical presentation, associated autoimmune conditions, autonomic and gastrointestinal dysmotility studies, GAD-Ab titers, and response to immunotherapy were recorded.

By chart review we identified 38 (25 female) non-diabetic patients with autonomic disorders and abnormal GAD-Abs.  Mean age 38 (range 14-75), 8 patients ≤ 18. Twenty-five were White, 4 Hispanic/Latino, 2 Black/African American, 2 Asian, and 5 Other. Four (10.5%) had peak titers >100 times the upper limit of normal (ULN), 10 (26%) >10-100x ULN, 7 (18%) >4-10x ULN, and 10 (26%) 2-4x ULN. Autonomic testing demonstrated several abnormalities with 13 demonstrating postural orthostatic tachycardia syndrome (POTS); 7 parasympathetic impairment; 7 abnormal valsalva ratio; 10 post-ganglionic sudomotor neuropathy. GI dysmotility symptoms were present in 29 patients (76%). Fourteen (36.8%) had systemic autoimmune conditions and 16 (42%) had other serum autoantibodies not associated with autonomic dysfunction. Nineteen (50%) underwent treatment immunotherapy (IVIG, PLEX, Rituximab) of which 10 (52%) improved clinically or on autonomic testing.