We present a case with coexisting GAD65 CNS autoimmunity and coincidental variants of uncertain significance (VUS) in the VPS13A gene which is associated with autosomal recessive chorea acanthocytosis. 

Glutamic Acid Decarboxylase (GAD) 65 spectrum disorder can present with a varying combination of abnormal movements and epilepsy. Autosomal recessive chorea acanthocytosis is a genetic disease that can result in movement disorders with epilepsy. 

A 46-year-old previously healthy African-American woman presented with adult-onset seizures. At onset, she experienced multiple brief dyscognitive seizures characterized by impaired awareness, nonsensical speech, and confusion daily. She had unremarkable birth and developmental history prior to seizure onset at age 35. Her sister has adult-onset epilepsy which is well-controlled on medication.  

Initial examination was normal. Interictal EEG showed only left temporal discharges initially. MRI and routine CSF studies were unremarkable. Despite multiple antiseizure medication trials seizures increased to vagal nerve stimulator implantation without sustained improvement. Eight years later, she developed choreoathetoid and dystonic movements in extremities and cerebellar ataxia. Testing for Huntington’s disease and inborn errors of metabolism was unrevealing. Serum and CSF autoimmune encephalopathy panels showed elevated GAD65 antibody titer values of 1140nmol/L and 0.92nmol/L, respectively. She was treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin leading to sustained improvements in symptoms with bi-annual rituximab infusions. Repeat MRI showed decreased volume of the left hippocampus. Repeat video-EEG monitoring showed independent bitemporal epilepsy leading to implantation of bilateral hippocampal responsive neurostimulators to help further improve seizure control. Whole exome sequencing revealed two VUSs in the VPS13A gene with additional testing of family members pending.   

GAD65 antibodies are not inherently pathogenic and are thought to be an epiphenomenon of inflammation or autoimmune processes. Our patient responded to immunomodulatory therapy despite coexistence of potential underlying genetic etiology suggesting that presence of high titer antibodies warrants a trial of immunotherapy.