Makindo Medical Notes

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

• GeneReviews: Ataxia-Telangiectasia
• Ataxia-Telangiectasia: Pathogenesis and Clinical Management – Lancet

💡 Exam Pearl

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