Ataxia-telangiectasia

Ataxia-telangiectasia (A-T), also known as Louis-Bar syndrome, is a rare, progressive, multisystem neurodegenerative disorder caused by biallelic pathogenic variants in the ATM gene (ataxia-telangiectasia mutated), located on chromosome 11q22.3. The ATM protein plays a critical role in DNA damage repair, cell cycle regulation, and immune function. A-T primarily affects the nervous system, immune system, and increases susceptibility to cancer. The hallmark features are progressive cerebellar ataxia, which typically becomes apparent when a child begins to walk (usually between ages 1 and 4), and oculocutaneous telangiectasias (small dilated blood vessels) that appear on the conjunctivae of the eyes and on sun-exposed skin areas, usually by age 5 to 8 years. As the disease progresses, children develop worsening gait and limb ataxia, dysarthria (slurred speech), oculomotor apraxia, choreoathetosis, and eventually most patients require wheelchair use by their teenage years. Immunodeficiency is common, affecting both humoral and cellular immunity, leading to recurrent sinopulmonary infections. Patients have a markedly increased risk of malignancies, particularly lymphomas and leukemias in childhood, and solid tumors later in life. Elevated serum alpha-fetoprotein (AFP) levels are a characteristic laboratory finding. Patients also exhibit increased sensitivity to ionizing radiation, which has important implications for diagnostic imaging and cancer treatment. There is currently no cure or disease-modifying therapy for A-T. Management is supportive and multidisciplinary, including physical and occupational therapy to maintain function, speech therapy, aggressive treatment of infections, immunoglobulin replacement therapy for those with significant antibody deficiency, and careful cancer surveillance. Importantly, radiation therapy should be avoided or used with extreme caution due to heightened radiosensitivity. Life expectancy is reduced, with many patients surviving into their twenties or thirties, though some individuals with milder (variant) forms may have longer survival. Research into targeted therapies, including antisense oligonucleotides and gene therapy approaches, is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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