Ataxia Telangiectasia is a rare, progressive, autosomal recessive disorder caused by mutations in the ATM gene (11q). It combines features of a neurodegenerative disorder, immunodeficiency, and cancer predisposition. 🧬

ATM gene encodes a protein kinase critical for DNA repair and cell cycle control. ⚡
Loss of ATM function → defective DNA repair, genomic instability, and radiation sensitivity. ☢️
Hallmark triad: progressive cerebellar ataxia, oculocutaneous telangiectasia, and immunodeficiency.

🧩 Aetiology & Pathophysiology

ATM mutation → defective phosphatidylinositol-3-kinase–related kinase function → impaired DNA double-strand break repair.
⛔ Cerebellar degeneration: loss of Purkinje & granular cells → progressive ataxia.
🦠 Immunodeficiency: T-cell and B-cell dysfunction → recurrent infections.
🎗️ Oncogenesis: markedly ↑ risk of lymphoid malignancies (esp. NHL, Hodgkin, leukaemia).
💨 Pulmonary complications: chronic chest infections → bronchiectasis.

👩‍⚕️ Clinical Presentation

🧒 Onset before age 10 with progressive neurological decline.
Ataxia: gait unsteadiness, poor coordination, frequent falls.
Apraxia of gaze: child turns head instead of moving eyes - highly suggestive exam clue 👀.
Movement disorders: chorea, athetosis, myoclonic jerks.
Telangiectasias: dilated vessels on bulbar conjunctiva & skin (e.g. ears, nose, cheeks). 🌐
Recurrent infections: sinusitis, pneumonia, bronchiectasis.
Endocrine: hypogonadism, delayed puberty.
Lymphadenopathy / fevers: possible lymphoma.

⚠️ Complications

🎗️ Very high risk of B-cell and T-cell lymphomas + leukaemias.
↑ risk of solid tumours, esp. breast and lung cancers (also in heterozygous carriers).
Chronic respiratory disease from recurrent infections.
Progressive neurodegeneration → severe disability.

🔎 Investigations

📈 Alpha-fetoprotein (AFP): elevated (diagnostic hallmark).
🧪 Immunoglobulins: ↓ IgA, IgE, IgG2, IgG4 (variable immune deficiency).
🧠 MRI Brain: cerebellar atrophy, enlarged 4th ventricle, widened sulci.
🧬 Genetic testing: confirms ATM mutations.

⚕️ Management

❌ No cure - treatment is supportive.
💊 Infection prevention: prophylactic antibiotics, IVIG replacement if severe hypogammaglobulinaemia.
🫁 Respiratory support: chest physiotherapy, bronchodilators, early treatment of infections.
🎗️ Cancer surveillance: close monitoring for lymphomas/leukaemias.
🧑‍🤝‍🧑 Genetic counselling: autosomal recessive inheritance; carriers have ↑ breast cancer risk.
⚠️ Avoid unnecessary radiation exposure (diagnostic & therapeutic) due to radiosensitivity.

📉 Prognosis

Life expectancy is limited - many patients do not survive beyond their early 20s due to infections or malignancy. Supportive multidisciplinary care (neurology, immunology, oncology, respiratory) is vital to improve quality of life.

📚 References

💡 Exam Pearl

Child with ataxia, ocular telangiectasia, recurrent infections, ↑AFP → think Ataxia-Telangiectasia. Always mention lymphoma risk and radiation sensitivity in exams. 🎯

The content on this website is provided for educational and informational purposes only to support exam preparation (e.g., MLA, MRCP, USMLE) and learning. This is NOT medical advice, diagnosis, treatment, or professional guidance. It does not replace consultation with a qualified healthcare professional, official guidelines (e.g., NICE, GMC, BNF), or supervised clinical practice. Always verify information with current, authoritative sources. Makindo and its contributors accept no liability for any reliance on this content, including errors, omissions, or any resulting harm, loss, or consequences. By using this site, you agree to these terms.

Ataxia Telangiectasia