Ataxia-Telangiectasia (A-T)

What causes A-T

A-T is caused by variants in both copies of the ATM gene. The ATM protein detects breaks in DNA and coordinates their repair. Without it, cells accumulate DNA damage, particularly in the cerebellum (the part of the brain that controls coordination), immune cells and blood-forming cells.

It is autosomal recessive: each parent carries one altered copy and usually has no symptoms. Each child of two carriers has a 25% chance of A-T, a 50% chance of being a carrier, and a 25% chance of neither. A-T is estimated to affect roughly 1 in 40,000 to 1 in 100,000 people.

Carriers of one ATM variant do not have A-T but have a moderately increased risk of breast cancer and some other cancers, and may need earlier screening.

Symptoms

Neurological

• Ataxia: wobbly, unsteady walking starting in the toddler years, often first thought to be normal clumsiness. Most children need a wheelchair by around the early teens.
• Abnormal eye movements: difficulty moving the eyes to look at something (oculomotor apraxia), so children turn their head first.
• Slurred speech (dysarthria) and drooling.
• Swallowing problems with risk of food entering the lungs.
• Involuntary movements: jerks, twisting postures or tremor.
• Intelligence is usually normal, though slow reactions can make learning harder.

Telangiectasia

Small, dilated red blood vessels appear on the whites of the eyes, usually between ages 3 and 6, and sometimes on the ears and cheeks. They are harmless but help confirm the diagnosis.

Immune system and lungs

• frequent sinus, ear and lung infections from low antibodies and T cells
• chronic lung disease from infections and aspiration
• interstitial lung disease in some people

Cancer risk

People with A-T have a high lifetime risk of cancer, roughly 1 in 4 to 1 in 3, most often leukemia and lymphoma in childhood and solid tumors in adulthood. Their cells are very sensitive to ionizing radiation, so X-rays and CT scans are limited, and cancer treatments must be adjusted.

Other features

• slow growth and delayed puberty
• early graying of hair and skin changes
• diabetes in adolescence or adulthood
• liver problems

Diagnosis

A-T is suspected in a child with progressive ataxia, especially with eye telangiectasia or frequent infections. Tests include:

• Alpha-fetoprotein (AFP): raised in nearly all people with A-T after age 2.
• Immune tests: antibody levels (IgA, IgG subclasses, IgE often low) and lymphocyte counts.
• Genetic testing of the ATM gene to confirm.
• ATM protein testing in specialized labs.
• MRI may show cerebellar shrinkage (used carefully, MRI does not use ionizing radiation).

A-T is one of several autosomal recessive cerebellar ataxias, alongside Friedreich ataxia and others, which doctors consider in a child with progressive unsteadiness.

Treatment and care

There is no treatment yet that stops progression. Care is coordinated by a multidisciplinary team:

• Physical, occupational and speech therapy to maintain mobility, independence and communication.
• Swallowing assessment and feeding support, including a gastrostomy tube if needed for nutrition and to protect the lungs.
• Infection prevention: immunoglobulin replacement for low antibodies, preventive antibiotics, and vaccines (live vaccines may be avoided depending on immune status).
• Lung care: airway clearance, monitoring lung function.
• Cancer surveillance and specialist oncology care, avoiding unnecessary radiation.
• Diabetes and liver monitoring in teens and adults.
• Educational support and adaptive equipment.
• Genetic counseling for the family.

Research into treatments such as dexamethasone delivered in red blood cells and gene-based therapies is ongoing.

Outlook

A-T is progressive. With improved infection control and specialist care, life expectancy has increased, and many people now live into their 20s and 30s or beyond, though it varies. Lung disease and cancer are the main causes of death.

Frequently asked questions

What are the first signs of ataxia-telangiectasia?

The first sign is usually unsteady, wobbly walking in a toddler, appearing between about ages 1 and 4 and becoming more noticeable over time. Red blood vessels in the whites of the eyes, slurred speech and frequent infections usually follow.

Is ataxia-telangiectasia inherited?

Yes. It is autosomal recessive, meaning a child must inherit a non-working ATM gene from both parents. When both parents are carriers, each pregnancy has a 1 in 4 chance of A-T.

What is the life expectancy with A-T?

Life expectancy varies widely. With modern care, many people with A-T live into their 20s or 30s, and some longer. Lung disease and cancers are the most common serious complications.

Why should people with A-T avoid X-rays?

Their cells cannot properly repair DNA damage caused by ionizing radiation, so X-rays, CT scans and radiotherapy carry higher risks. Doctors use ultrasound or MRI where possible and adjust cancer treatment doses.