The first manifestation of the disease (usually candidiasis) occurs in childhood with other manifestations appearing progressively. Candidiasis affects particularly the mucosa of the mouth, nails and, more rarely, the genitals, and rarely causes cutaneous effects. The most common autoimmune endocrine involvement is hypoparathyroidism (79-96% of cases). Adrenal failure most often manifests with concurrent mineralocorticoid and glucocorticoid deficiency (78% of cases). Ovarian failure is possible. Diabetes type 1, autoimmune thyroiditis, and lymphocytic hypophysitis are rarer. Other auto-immune manifestations are common: intestinal malabsorption, atrophic gastritis, autoimmune hepatitis, alopecia, vitiligo, hypoplasia of dental enamel, ungual dystrophy, keratoconjunctivitis, and rheumatologic, bony, muscular, renal, bronchiol and hematologic impairments. Splenic atrophy increases the likelihood for severe infections. There is high phenotypic variability, sometimes within the same family, and the number of manifestations is very variable, ranging from 1 to 10.
The disease is caused by mutations of the AIRE gene (21q22.3) coding for the AIRE transcription factor, which is involved in immune tolerance mechanisms and contributes to the negative selection of autoreactive T lymphocytes in the thymus, lymph nodes and spleen.
