Ataxia telangiectasia

Ataxia telangiectasia is an autosomal recessive trait in which affected individuals have a progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies, and immunodeficiency (Shiloh and Rotman 1996).

Genetic

The gene is on chromosome 11 (11q22–q23) and has been cloned (ataxia telangiectasia mutated gene, ATM). The defective gene encodes an enzyme (very like phosphoinositol 3-kinase) which is responsible for repair of DNA damage and cell control. About 1 per cent of the population are heterozygotes for this gene, and have a two- to sixfold greater risk of developing cancer (Morrell et al. 1990; Swift et al. 1991).

Homozygotes are 100 times more likely to develop cancer than age-matched controls (Morrell et al. 1990). The ataxia telangiectasia gene is associated with a sensitivity to ionizing radiation and homozygotes can develop tissue necrosis when exposed to conventional therapeutic doses of radiation. It is thought that diagnostic or occupational exposure to radiation increases the risk of cancer in these individuals.

Morphology and diagnostics

Ataxia telangiectasia is the common cause of progressive ataxia in childhood, and usually manifests itself by the age of 3 years, when most cases have some element of truncal ataxia.

Other skin changes such as hypopigmentation or hyperpigmentation and premature greying of hair are commonly found. There is commonly an ocular dyspraxia, with nystagmus and frequent blinking. There is an increased incidence of sinus infections and respiratory infections, with bronchiectasis and lung abscesses related to deficiencies in serum immunoglobulins (especially IgA). Hypogonadism, growth failure with normal growth hormone levels, and diabetes mellitus, which may be insulin resistant, also occur (Woods and Taylor 1992).

Diagnosis is usually evident on clinical grounds, although the telangiectasias may appear after the ataxia has been present for some time.

  • Serum α-fetoprotein is increased in 90% and some patients also have elevated carcinoembryonic antigen (Woods and Taylor 1992).
  • Serum immunoglobulins (IgA, IgE, IgG2) are decreased or absent, while IgM is normal or elevated.

Genetic linkage studies may be helpful if many family members are available.

Management

Management involves treatment of intercurrent infections with physiotherapy and antibiotics and being aware that, if cancers are found, conventional doses of radiation will be highly toxic and are contraindicated. Vaccination with live virus vaccines are also to be avoided (Pohl et al. 1992).