Objective: In this study we show a couple of siblings with a progressive cerebellar ataxia associated with mutation in MRE11A. Our goal is to demonstrate the importance of Ataxia-Telangiectasia-Like-Disorder (ATLD) in the context of ataxia in childhood.

Background: Ataxia-telangiectasia (AT) is an important cause of ataxia in childhood. Some patients have a phenotype that is not associated with mutation in ATM gene, which has been called ATLD. Pathogenic variants of the MRE11A gene is the main gene associated with ATLD. An 8-year-old girl presented with slowly progressive instability of gait with clinical onset at the age of 24 months. She was the first child of non-consanguineous parents and was born full term with no complications. The patient’s sibling, a 5-year-old boy, presented with imbalance in gait since 36 months, without worsening over time.

Method: On neurological examinationshe exhibited mild muscle hypotonia, ataxia, choreoathetosis, distal muscular amyotrophy and dystonia in hands and feet, with absence of dysmorphic signs. Eyes movements reveled oculomotor apraxia. Serum vitamins, metabolites, immunoglobulin, evaluation for innate metabolism error, liver, thyroid and kidney functions were unremarkable, including brain magnetic resonance imaging. Electroneuromyography showed axonal sensitive polyneuropathy. Lastly, it was performed a whole exome on the girl. Regarded to the boy, he is unable to walk in a straight line, without other signs or symptoms.

Results: It was identified two heterozygous variants in the MRE11A gene (p.Glu506 and p.Lys660Thr fs 45) associated with ATLD. MRE11A gene sequencing was performed on the boy, which identified the same mutation.

Conclusion: The clinical features of the majority of patients with ATLD resemble those patients with AT including progressive cerebellar ataxia, oculomotor apraxia, and cellular hypersensitivity to ionizing radiations, with a milder and slower presentation, whereas telangiectasia, immunodeficiency, and increased α-fetoprotein have not been reported. In this context, ATLD associated with MRE11A mutation should be considered in childhood ataxia.

References: 1) Taylor AM, Groom A, Byrd PJ. Ataxia-telangiectasia-like disorder (ATLD)— its clinical presentation and molecular basis. DNA Repair (2004) 3:1219–25. 2) Stracker TH, Petrini JHJ. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol (2011) 12:90–103. 3) Stracker TH, Roig I, Knobel PA, Marjanović M. The ATM signaling network in development and disease. Front Genet. 2013, 4:37 4) Verhagen MM, Abdo WF, Willemsen MA, Hogervorst FB, Smeets DF, Hiel JA, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology (2009) 73:430–7. 5) Uchisaka N, Takahashi N, Sato M, Kikuchi A, Mochizuki S, Imai K, et al. Two brothers with ataxia-telangiectasia-like disorder with lung adenocarcinoma. J Pediatr (2009) 155:435-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/two-cases-of-ataxia-telangiectasia-like-disorder-phenotypic-spectrum-associated-with-mre11-gene/