Ataxia telangiectasia (A-T) is a rare primary immunodeficiency that affects the nervous system, the immune system, and many other parts of the body. The condition is typically characterized by early childhood onset of cerebellar ataxia, oculomotor apraxia, telangiectasias, choreoathetosis, a weakened immune system with frequent infections, and an increased risk of cancers such as leukemia and lymphoma.
Etiology
A-T is caused by changes in the ATM gene located on chromosome 11q22-23 and is inherited in an autosomal recessive manner. The ATM gene is responsible for encoding serine/threonine protein kinase, which when impaired causes abnormal repairing of the breaks in the DNA. This causes impaired cell responses to pathogenic triggers and leads to cell death.
Signs and Symptoms
The first signs of A-T are typically cerebellar ataxia, dilated capillaries in the oculocutaneous region (telangiectasias), and truncal instability. These often occur in the first decade of life. Common signs and symptoms also include:
- Dysarthria
- Oculomotor apraxia
- Extrapyramidal symptoms
- Axonal neuropathy
- Cognitive impairment
- Immunological and endocrine abnormalities
Additionally, patients with A-T experience higher risk of neoplastic disease, as well as elevated serum levels of alpha-fetoprotein. Tumors are occasionally reported in patients with A-T.
Diagnosis
Diagnosis of A-T typically follows findings in clinical presentation, neuroimaging, laboratory tests, and genetic testing. Usually, these patients present with ataxia, oculomotor apraxia, telangiectasias, cerebellar atrophy, alpha-fetoprotein elevation, and genetic abnormalities in the ATM gene.
Management Strategies and Treatment
Currently, there are no treatments that target the underlying cause of A-T. Treatments tend to focus on individualized symptom management. This includes physical therapy and mobility aids, treatment of recurrent infections, and treatment targeting tumors.
Clinical trials are currently investigating the use of antioxidants, antisense morpholino oligonucleotides, and aminoglycoside antibiotics that can target ATM protein function.
Clinical Trials and Studies
For a full list of clinical trials relating to ataxia telangiectasia, click here.
Resources
References
Riboldi GM, et al. Ataxia-Telangiectasia. [Updated 2024]. In: StatPearls [Internet]. Available at https://www.ncbi.nlm.nih.gov/books/NBK519542/
For more information on rare neurological disorders, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/
