Summary

Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the ATM (ataxia-telangiectasia mutated) gene, which encodes a protein kinase critical for DNA double-strand break repair. The condition is characterised by the classic triad of progressive cerebellar ataxia, oculocutaneous telangiectasias, and immunodeficiency. A-T typically presents in early childhood with gait instability, and follows a progressive course leading to wheelchair dependence by adolescence. Affected individuals have markedly increased cancer susceptibility (especially lymphoid malignancies) and extreme radiosensitivity. Life expectancy is significantly reduced, with most patients dying in their second or third decade from respiratory failure or malignancy.

Key Facts

• Inheritance: Autosomal recessive (ATM gene on chromosome 11q22-23)
• Incidence: 1 in 40,000-100,000 live births
• Classic Triad: Ataxia + Telangiectasia + Immunodeficiency
• Cancer Risk: 50-fold increased; lymphoma/leukaemia most common
• Radiosensitivity: Extreme; avoid unnecessary X-rays and radiotherapy
• Prognosis: Median survival 19-25 years

Clinical Pearls

The Hidden Triad: Telangiectasias may not appear until age 5-8 years, so early A-T may present as isolated progressive ataxia. Consider A-T in any child with progressive cerebellar ataxia and recurrent infections.

Alpha-Fetoprotein Clue: Elevated serum AFP (90% of patients) is a useful diagnostic marker — unique among the ataxias.

Radiation Danger: A-T patients are exquisitely radiosensitive. Avoid unnecessary imaging and NEVER give radiotherapy without discussing with A-T specialists.

Why This Matters Clinically

A-T is a multi-system disorder requiring coordinated care across neurology, immunology, pulmonology, and oncology. Early recognition enables appropriate supportive care, infection prevention, and cancer surveillance. ATM heterozygotes (carriers) also have increased cancer risk, with implications for genetic counselling.

Structured Approach

General:

• Short stature
• Progeria-like features
• Conjunctival telangiectasias (bilateral)
• Skin telangiectasias (ears, antecubital fossae)

Neurological:

• Cerebellar signs: broad-based gait, intention tremor, dysmetria, dysdiadochokinesia
• Oculomotor apraxia: head thrust to initiate saccades
• Dysarthria
• Choreoathetosis
• Peripheral neuropathy (later): reduced reflexes, sensory loss

Respiratory:

• Signs of chronic lung disease
• Clubbing (bronchiectasis)

Special Tests

Natural History

• Progressive neurological decline
• Wheelchair dependence typically by 10-15 years
• Increasing respiratory complications

Life Expectancy

Quality of Life

• Intelligence often preserved
• Fatigue from chronic illness
• Significant impact on mobility and independence
• Psychosocial support essential

Key Guidelines

1. A-T Clinical Guidance Document — A-T Society (USA).
2. ESID Guidelines for Primary Immunodeficiencies — European Society for Immunodeficiencies.
3. UK A-T Clinical Care Guidance — A-T Society (UK).

Key Evidence

Rothblum-Oviatt et al. (2016) — A-T Clinical Care Guidelines

• Comprehensive consensus guidelines for management
• PMID: 27066985

Swift et al. (1991) — ATM Heterozygotes and Cancer

• ATM carriers have increased breast cancer risk
• PMID: 1985460

Evidence Strength

What is Ataxia Telangiectasia?

Ataxia telangiectasia (A-T) is a rare genetic condition that affects movement, the immune system, and other parts of the body. It is caused by a faulty gene (ATM) that normally helps repair damaged DNA.

What are the main features?

1. Ataxia: Difficulty with balance and coordination, starting in early childhood. This gets worse over time.
2. Telangiectasias: Tiny red blood vessels that appear on the eyes and skin (usually after age 5).
3. Weak immune system: This leads to frequent chest and sinus infections.
4. Cancer risk: Higher risk of developing certain cancers, especially leukaemia and lymphoma.

How is it treated?

There is no cure, but treatment focuses on:

• Preventing and treating infections (antibiotics, sometimes immunoglobulin infusions)
• Chest physiotherapy to keep the lungs clear
• Physiotherapy to maintain movement and strength
• Avoiding unnecessary X-rays and radiation

What to expect

• A-T is a progressive condition
• Most children will need a wheelchair by their teenage years
• With good care, quality of life can be maintained
• Life expectancy is reduced but improving with better care

When to seek help

See a doctor urgently if your child has:

• Frequent chest infections or breathing problems
• Unusual tiredness, weight loss, or lumps (could indicate cancer)
• Difficulty swallowing