Autoimmune polyendocrinopathy syndrome

Autoimmune polyendocrinopathy syndrome: A genetic autoimmune disease with an extraordinary array of clinical features but characterized most often by at least 2 of the following 3 findings: hypoparathyroidism — underfunction of the parathyroid glands which control calcium, candidiasis (yeast infection), and adrenal insufficiency (underfunction of the adrenal gland). The autoimmune polyendocrinopathy syndrome was the first systemic (bodywide) autoimmune disease found due to a defect in a single gene.

By “autoimmune” is meant that the immune system (which normally wards off foreign invaders of the body) turns and attacks tissues such as skin, joints, liver, lungs, etc.) of the body. Examples of common systemic autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, diabetes mellitus, Sjogren syndrome, scleroderma, Goodpasture syndrome, vitiligo, Addison disease, thyroiditis, and many others.

In 1997 a novel gene was identified that mapped to chromosome region 21q22.3. The gene was named AIRE for autoimmune regulator. Changes in the AIRE gene are responsible for the autoimmune polyendocrinopathy syndrome.

The syndrome is inherited as a recessive trait such that a child with the disease has received 2 changed (mutant) AIRE genes, one from each parent. Although the syndrome is generally rare, it is more frequent in 3 genetically isolated populations: the Finnish, Iranian Jews, and Sardinians.

The child with autoimmune polyendocrinopathy syndrome develops problems in numerous glands (polyendocrine) including hypoparathyroidism, hypogonadism (with sex gland failure), adrenal insufficiency, type 1 (insulin-dependent) diabetes with insufficient insulin production by the pancreas gland, and latent hypothyroidism (underfunction of the thyroid gland). Other features of the autoimmune polyendocrinopathy syndrome are total baldness (alopecia totalis), inflammation of the cornea and whites of the eye (keratoconjunctivitis), underdevelopment (hypoplasia) of the enamel of the teeth, childhood-onset moniliasis (yeast infection), juvenile-onset pernicious anemia, gastrointestinal problems (malabsorption, diarrhea), and chronic active hepatitis.

The laboratory studies attest to an immune disease with an abnormally low level of gammaglobulin antibodies in blood (hypogammaglobulinemia) and an abnormally low T4/T8 white blood cell ratio (as in AIDS). There is specific evidence for autoimmunity with antibodies directed against the adrenal and thyroid glands and against cell nuclei (antiadrenal, antithyroid and antinuclear antibodies).

The treatment of the autoimmune polyendocrinopathy syndrome is directed at treating the specific problems: replacing the various hormones that are in short supply, giving insulin for the diabetes, treating the yeast infections, etc. However, there is no known cure for the autoimmune polyendocrinopathy syndrome.

The prognosis (outlook) depends on whether the critical hormone deficiencies are remedied and especially whether the infections can be successfully controlled.

The autoimmune polyendocrinopathy syndrome goes by a confusing array of other names including autoimmune polyglandular syndrome (APS), polyglandular autoimmune syndrome (PGA), autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), hypoadrenocorticism with hypoparathyroidism and superficial moniliasis, and polyglandular deficiency syndrome.