Objective: Here we present a case of ataxia and muscle stiffness in a person with variant EEF2 gene mutation with associated anti-GAD antibodies along with a history of autoimmune conditions.

Background: EEF2 gene mutation which is autosomal dominant has been linked to a rare spinocerebellar ataxia (SCA 26) which typically presents in adulthood with pure cerebellar symptoms and mean age of onset of 42 years (Yu, 2005). A few pediatric cases with de novo mutations of EEF2 gene were reported which present with development delay, autism spectrum disorder, cerebellar symptoms (Zhao 2022, Prasun 2024). In addition, anti-glutamic acid decarboxylase (anti-GAD) autoantibodies are associated with several neurological syndromes, including cerebellar ataxia (Graus 2020). Cerebellar ataxia has also been associated with autoimmune conditions and at least one previous case of CVID associated cerebellar ataxia has been reported (Nguyen 2020).

Method: Here is a case of a 41-year-old female who presented with a history of unusual movements predominantly affecting her right arm and trunk. She noticed in her 20s that when she walked her right arm “started moving.”  Examination revealed a dystonic tremor and ataxia, associated with muscle spasms and stiffness.  She could suppress these movements by tensing certain muscle groups or maintaining specific postures. She later noted painful muscle spasms particularly in the right chest and upper back as well as anorectal spasms, which led to a colostomy. At the time of presentation, she had a diagnosis of Celiac disease and Common Variable Immunodeficiency (CVID) and had been receiving IVIG.  When she first started treatment, her abnormal movements completely resolved.  She had briefly paused IVIG treatment and noted a worsening of these movements. A trial of several Botox sessions failed to improve her dystonic tremor. At age 44, she underwent genetic testing. She continued to receive IVIG and physical therapy, but the movements have persisted.

Results: GAD-65 antibody level was 37 (normal <5 IU/mL), obtained 3 months after her last IVIG session. Her MRI brain was normal. The dystonia panel, microarray panel, and mitochondrial genetic testing that were negative. Whole exome sequencing revealed a variant EEF2 gene.

Conclusion: Here we present a case of adult-onset ataxia and muscle stiffness which could be multifactorial in the setting of EEF2 gene mutation and anti-GAD cerebellar ataxia.

References: Dalakas MC. Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies. Neurotherapeutics. 2022 Apr;19(3):832-847. doi: 10.1007/s13311-022-01188-w. Epub 2022 Jan 27. PMID: 35084720; PMCID: PMC9294130.

Graus F, Saiz A, Dalmau J. GAD antibodies in neurological disorders – insights and challenges. Nat Rev Neurol. 2020;16: 353–365.

Guo R, Rippert AL, Cook EB, Alves CAP, Bird LM, Izumi K. Expansion of clinical and variant spectrum of EEF2-related neurodevelopmental disorder: Report of two additional cases. Am J Med Genet A. 2023 Oct;191(10):2602-2609. doi: 10.1002/ajmg.a.63230. Epub 2023 May 9. PMID: 37159414; PMCID: PMC10527330.

Nguyen T, McCauley M, Zheng T, Rizvi SA. Common Variable Immunodeficiency Presenting as Anti-GAD Cerebellar Ataxia. R I Med J (2013). 2020 Dec 1;103(10):38-39. PMID: 33261233.

Prasun, Pankaj, Patra, Kamakhya; EEF2-Related Neurodevelopmental Disorder Is Clinically Recognizable. Mol Syndromol 1 October 2024; 15 (5): 403–408. https://doi.org/10.1159/000538059

Yu, G.-Y., Howell, M. J., Roller, M. J., Xie, T.-D., Gomez, C. M. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann. Neurol. 57: 349-354, 2005

Zhao H, Mata-Machado N (July 14, 2022) A Comparison of Pathogenic Eukaryotic Elongation Factor 2 (EEF2) Variants in Spinocerebellar Ataxia 26 Versus De Novo Mutations. Cureus 14(7): e26857. doi:10.7759/cureus.26857

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-case-of-ataxia-and-muscle-stiffness-in-eef2-gene-mutation-with-associated-anti-gad-antibodies/