Ataxia-telangiectasia results from a DNA repair defect that frequently results in humoral and cellular deficiency; it causes progressive cerebellar ataxia, oculocutaneous telangiectasias, and recurrent sinopulmonary infections.
Inheritance is autosomal-recessive. Estimated incidence is 1 in 20,000 to 100,000 births. Ataxia-telangiectasia is caused by mutations in the gene that encodes ataxia-telangiectasia–mutated (ATM) protein. ATM is involved in detection of DNA damage and helps control the rate of cell growth and division. Patients often lack IgA and IgE and have a progressive T-cell defect.
Symptoms and Signs
Age at onset of neurologic symptoms and evidence of immunodeficiency vary.
Ataxia is frequently the first symptom and usually develops when children begin to walk. Progression of neurologic symptoms leads to severe disability. Speech becomes slurred, choreoathetoid movements and nystagmus develop, and muscle weakness usually progresses to muscle atrophy.
Telangiectasias may not appear until age 4 to 6 yr; they are most prominent on the bulbar conjunctivae, ears, antecubital and popliteal fossae, and sides of the neck.
Recurrent sinopulmonary infections lead to recurrent pneumonia, bronchiectasis, and chronic restrictive pulmonary disease.
Certain endocrine abnormalities (eg, gonadal dysgenesis, testicular atrophy, diabetes mellitus) may occur.
Frequency of cancer (especially leukemia, lymphoma, brain tumors, and gastric cancer) is high. Cancer typically occurs after age 10 and at a rate of about 1%/yr but is a lifelong risk and can occur at any age.
Clinical findings of cerebellar ataxia (particularly when telangiectasias are present), low levels of IgA (present in 80% of patients with this disorder), and high levels of serum α1-fetoprotein suggest the diagnosis. If karyotype analysis is done, chromosome breaks, consistent with a defect in DNA repair, are often seen. Diagnosis is confirmed by identifying mutations on both alleles of the gene for ATM protein. Because carriers of an AT mutation usually remain asymptomatic, testing siblings for a carrier state can help predict their chance of having an affected child.
Testing for endocrine abnormalities and cancers is done based on clinical presentation.
Treatment with prophylactic antibiotics or IV immune globulin may help. In one small study, treatment with amantadine resulted in minimal improvement in motor function, but there is no effective treatment for the progressive neurologic deterioration, which causes death, usually by age 30.
Chemotherapy is often indicated for treatment of associated cancers.
Last full review/revision November 2013 by James Fernandez, MD, PhD
Content last modified November 2013