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.
Ataxia-telangiectasia is an autosomal-recessive primary immunodeficiency disorder that involves combined humoral and cellular deficiencies. 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.
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.
The following clinical findings suggest the diagnosis of ataxia-telangiectasia:
If karyotype analysis is done, chromosome breaks, consistent with a defect in DNA repair, are often seen.
Diagnosis of ataxia-telangiectasia is confirmed by identifying mutations on both alleles of the gene for ATM protein. Because carriers of an ataxia-telangiectasia 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 immune globulin may help patients with ataxia-telangiectasia.
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.