Ann IM 1983;99:367; Nejm 1979;300:702

Cause:Genetic, autosomal recessive (Nejm 1995;333:662)

Pathophys:Diabetes due to defective insulin receptors (Nejm 1978;298:1124). Ataxia due to damage to posterior columns and anterior horn cells. The immunodeficiency is caused by a failure of a DNA "glue" enzyme in both T and B lymphocytes to switch from acute responses (eg, IgM) to chronic immune defense (eg, IgG) (Nejm 1990;322:124)

80% lack IgA and thymus; a form of dysgammaglobulinemia type III with decreased or absent IgA, IgE, and 2 subsets of IgG. 1-7% gene prevalence in the US

Sx:Amenorrhea (no ovaries); recurrent sinopulmonary infections (no IgA)

Si: Oculocutaneous telangiectasias, impaired delayed hypersensitivity problems, progressive neurologic dysfunction, ataxia, acanthosis nigricans (Nejm 1978;298:1164)

Onset usually as learn to walk w subsequent choreoathetosis, dysarthria, abnormal eye movements, etc

Even carriers have a 8-yr shortened life expectancy (Ann IM 2000;133:770)

Increased incidence of many neoplasms, esp of the immune tissues, and especially of T-cell origin (Nejm 1979;300:700). And breast cancer, in patients with HAT, as well as in those who are heterozygous carriers; represents 9% of all US breast cancer (Nejm 1987;316:1289); exposure to radiation, eg, mammograms, may markedly increase the incidence in HAT patients as well as heterozygotes (Nejm 1991;325:1831). Also increased colon, lung, prostate, and pancreatic cancers

Insulin-resistant diabetes

Lab:Serol:IgA, IgE, IgG₂, and IgG₄ usually are absent; increase in IgM and ₁-fetoglobulin (r/o embryonal cell cancers and CEA)

Rx:Avoid xrays and radiation rx (Nejm 1991;325:1831) in these patients and close blood relatives