Objective: To make the first case report of the association between Anti-GAD and parkinsonism.

Background: GAD (Glutamic Acid Decarboxylase) is the enzyme that catalyzes the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) from glutamate. Anti-GAD Antibodies limit the speed of GABA synthesis by targeting this rate limiting enzyme of GABA synthesis. They are directed against its two isoforms in mammals (GAD65 and GAD67) which are present in pathologies such as stiff-person syndrome and variants, stiff leg syndrome, insulin-dependent diabetes mellitus, cerebellar ataxia, limbic and extra-limbic encephalitis, progressive encephalopathy with limb rigidity (PERM), oculomotor dysfunction and drug-resistant epilepsy. Until our latest search there have not been any reported cases of anti-GAD and parkinsonism.

Method: We report a case of a 54-years old Latin female patient with one year of past medical history of headaches, anxiety, dysthymia, cognitive impairment, freezing gate, paresis, pruritus, loss of strength, extremities claudication, rigidity, tremor, bradykinesia, and dysbasia.  
At physical examination, she was found to have memory loss, hyperreflexia, Hoffman’s, Romberg´s, frontal release signs, eyelid ptosis, afferent pupillary reflex, nystagmus, right upper extremity tremor, right side stiffness with cogwheel rigidity predominantly in right side, fasciculations, ataxia and difficulties with tandem gate. MRI showed hyperintensities in insular and parietal cortices, and demyelinating lesions in left insula. After further investigation blood work showed positive Anti-GAD, ANA and anti-dsDNA.

Results: Patient initially received dopamine agonist and symptomatic treatment with minimal response; after positive lab results immune therapy was initiated with partial response, MTP, ANA and anti-dsDNA became negative, but GAD remained positive. Patient remained with rigidity on the right side. Due to latest results she was started on anti-CD20 therapy with better clinical response.

Conclusion: This is the first case of parkinsonism due to Anti-GAD. GABA deficiency due to Anti-GAD positivity can be a main cause of symptoms and signs in Parkinsonism. Autoimmunity factors can be regulated by immunomodulatory therapy such as anti CD20 therapy. We recommend that anti-GAD should be looked for in the presence of possible parkinsonism.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-glutamic-acid-decarboxylase-antibodies-anti-gads-and-parkinsonism-case-report/