Ataxia-telangiectasia results from a T-cell defect and causes progressive cerebellar ataxia, oculocutaneous telangiectasias, and recurrent sinopulmonary infections.
Inheritance is autosomal-recessive. Ataxia-telangiectasia is caused by mutations in the gene that encodes ataxia-telangiectasia–mutated (ATM) protein. ATM protein may be important in mitogenic signal transduction, meiotic recombination, and cell cycle control.
Age at onset of neurologic symptoms and evidence of immunodeficiency vary. Ataxia 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. Patients often lack IgA and IgE and have a progressive T-cell defect. Certain endocrine abnormalities (eg, gonadal dysgenesis, testicular atrophy, diabetes mellitus) may occur.
Frequency of cancer (especially leukemia, brain tumors, and gastric cancer) is high, and frequency of chromosome breaks, consistent with a defect in DNA repair, is increased. Serum α1-fetoprotein is usually elevated.
Clinical findings of cerebellar ataxia (particularly when telangiectasias are present), low levels of IgA, and high levels of serum α1-fetoprotein suggest the diagnosis. Diagnosis is confirmed by identifying mutations on both alleles of the gene for ATM protein.
Treatment with antibiotics or IV immune globulin may help, but no treatment is effective for the CNS abnormalities. Thus, neurologic deterioration progresses, causing death, usually by age 30.
Last full review/revision September 2008 by Rebecca H. Buckley, MD