Stiff Person Syndrome - Causes

Causes

Because many patients with SPS have circulating antibodies to the enzyme glutamic acid decarboxylase (GAD), an autoimmune cause of the disease has been postulated. However, GAD antibodies cannot be the sole cause, as most Type I diabetics possess anti-GAD antibodies, yet the frequency of SPS among Type I diabetics is 1 in 10,000. Approximately 60% of patients diagnosed with SPS have anti-GAD antibodies present, while 40% do not and therefore rely on clinical testing for diagnosis. The GAD protein regions (epitopes) recognized by these antibodies may differ in each disease(GAD65ab). A mutation in GLRA1 (glycine receptor) is responsible for some cases of stiff person syndrome. Apart from antibodies to GAD65 seen in the serum, these antibodies are also found in the cerebrospinal fluid of stiff-person syndrome patients. Rarely, SPS is associated with breast cancer and Hodgkin's lymphoma.