Ataxia-telangiectasia

Ataxia-telangiectasia
Classification and external resources

Ataxia-telangiectasia (A-T) is a rare, neurodegenerative, inherited disease that affects multiple systems in the body. It is characterized by progressive difficulty with movement coordination (ataxia), dilated blood vessels (telangiectasia), and a weakened immune system.

Etiology

Ataxia-telangiectasia is caused by mutations in the ATM gene (Ataxia Telangiectasia Mutated), which is located on chromosome 11. The ATM gene is responsible for coding a protein that plays a crucial role in the repair of DNA double-strand breaks. Mutations in this gene lead to the accumulation of DNA damage, contributing to the symptoms of the disease.

Clinical Features

The hallmark features of A-T include:

• Ataxia: This is often the first symptom to appear, usually in early childhood. It manifests as a lack of voluntary coordination of muscle movements, leading to difficulties with walking, balance, and fine motor skills.

• Telangiectasia: These are small, dilated blood vessels that become visible in the eyes and on the skin, particularly on the face.

• Immunodeficiency: Patients with A-T have a higher susceptibility to infections, particularly of the respiratory system, due to a weakened immune response.

• Increased Cancer Risk: Individuals with A-T have a significantly increased risk of developing cancers, particularly lymphoma and leukemia.

Diagnosis

Diagnosis of ataxia-telangiectasia is based on clinical evaluation, family history, and genetic testing to identify mutations in the ATM gene. Laboratory tests may show elevated levels of alpha-fetoprotein (AFP) in the blood, which is a common finding in A-T patients.

Management

There is currently no cure for ataxia-telangiectasia. Management focuses on supportive care and symptomatic treatment:

• Physical Therapy: To help maintain mobility and manage ataxia.
• Immunoglobulin Replacement Therapy: For patients with significant immunodeficiency to help prevent infections.
• Regular Monitoring: For early detection and treatment of infections and cancers.

Prognosis

The prognosis for individuals with ataxia-telangiectasia varies. Many patients experience a progressive decline in neurological function and have a reduced lifespan, often due to respiratory complications or cancer.

Research

Ongoing research is focused on understanding the molecular mechanisms of ATM gene mutations and developing potential therapies, including gene therapy and drugs that can enhance DNA repair mechanisms.

See Also

• Neurodegenerative disease
• Genetic disorder
• Immunodeficiency

References

• Gatti, R. A., & Perlman, S. (2003). Ataxia-telangiectasia. In GeneReviews® [Internet]. University of Washington, Seattle.
• Rothblum-Oviatt, C., Wright, J., Lefton-Greif, M. A., McGrath-Morrow, S. A., Crawford, T. O., & Lederman, H. M. (2016). Ataxia telangiectasia: a review. Orphanet Journal of Rare Diseases, 11(1), 1-21.