Ataxia-telangiectasia

Overview

Ataxia-Telangiectasia (A-T) is a rare, inherited neurodegenerative disorder that affects multiple systems in the body. It is primarily characterized by progressive cerebellar ataxia (lack of muscle coordination), telangiectasias (small dilated blood vessels), immune system deficiencies, and a significantly increased risk of cancer—particularly leukemia and lymphoma. Symptoms typically begin in early childhood and worsen over time.

A-T is one of the classic “chromosome instability syndromes” and results from a defect in DNA repair mechanisms, making patients highly sensitive to ionizing radiation and prone to genomic instability.

Causes

Ataxia-Telangiectasia is caused by mutations in the ATM gene (Ataxia Telangiectasia Mutated), located on chromosome 11. The ATM gene encodes a protein involved in the detection and repair of damaged DNA. When this gene is mutated, the body cannot efficiently repair DNA breaks, leading to cell death in neurons and increased cancer risk due to genomic instability.

The disorder is inherited in an autosomal recessive pattern, meaning a child must inherit two mutated copies of the ATM gene (one from each parent) to develop A-T.

Symptoms

Symptoms of Ataxia-Telangiectasia typically appear in early childhood and progressively worsen. Major clinical features include:

Neurological Symptoms (Cerebellar Ataxia):

• Unsteady gait (usually begins between ages 1–4)

• Difficulty with fine motor tasks (e.g., writing, buttoning)

• Slurred speech (dysarthria)

• Oculomotor apraxia (difficulty moving eyes voluntarily)

• Involuntary movements (chorea, myoclonus)

Telangiectasias:

• Prominent on the whites of the eyes (conjunctiva)

• Also found on ears, face, and sun-exposed areas

Immune System Deficiency:

• Frequent respiratory infections

• Sinopulmonary complications (bronchiectasis, chronic lung disease)

Increased Cancer Risk:

• Especially non-Hodgkin lymphoma, leukemia, and other solid tumors

Other Features:

• Growth retardation and delayed puberty

• Elevated alpha-fetoprotein (AFP) levels in blood

• Radiation sensitivity

Diagnosis

Diagnosis is based on a combination of clinical features, laboratory tests, and genetic confirmation:

• Physical exam: Reveals ataxia, eye telangiectasias, and developmental delay

• Alpha-fetoprotein (AFP): Elevated in >90% of patients

• Immunoglobulin levels: Low IgA and/or IgG2 in many cases

• Genetic testing: Confirms mutations in the ATM gene

• MRI: May show cerebellar atrophy

• Cellular tests: Increased chromosomal breakage or sensitivity to radiation exposure

Treatment

There is currently no cure for Ataxia-Telangiectasia. Treatment focuses on managing symptoms, preventing infections, and reducing cancer risk:

Neurological Management:

• Physical therapy to preserve mobility

• Occupational and speech therapy

• Assistive devices for walking and communication

Immunologic Support:

• Immunoglobulin replacement therapy (IVIG or SCIG)

• Prophylactic antibiotics for recurrent infections

Cancer Surveillance:

• Regular screenings for lymphoma and leukemia

• Minimization of diagnostic radiation exposure

Supportive Care:

• Feeding support or gastrostomy in cases of swallowing difficulties

• Psychosocial support for family and caregivers

Prognosis

Ataxia-Telangiectasia is a progressive condition, and most patients become wheelchair-dependent in adolescence. Life expectancy is significantly reduced, with many individuals living into their 20s or 30s. However, with modern supportive care, some patients live longer into adulthood.

• Main causes of early death: Cancer and chronic lung disease

• Carrier status: Parents and siblings carrying one ATM mutation may have a slightly increased risk of breast or other cancers

Early diagnosis, multidisciplinary care, and genetic counseling are essential to improving outcomes and providing guidance to affected families.