Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy (APECED) [84.8]

OMIM numbers: 240300607358 (AIRE)

Dr. rer. nat. Christoph Marschall

Scientific Background

APECED is currently the only known autoimmune disorder that is inherited in a monogenic manner. It follows an autosomal recessive inheritance pattern. The AIRE gene (autoimmune regulator) was identified as cause. The disorder manifests already during childhood and is characterized by at least two of the following major signs:

  • Addison's disease
  • Hypoparathyroidism
  • Chronic candidiasis of the skin and mucous membranes without generalized infestation

Additional endocrine disorders, e.g. diabetes mellitus type 1, thyroiditis and hypergonadotropic hypogonadism, caused by autoimmune processes develop facultatively. The autoimmunologic changes may also affect other organs, which may result in disorders such as dystrophy of ectodermal structures (dystrophies of the dental enamel and nails, alopecia, vitiligo, keratopathy), pernicious anemia in chronic atrophic gastritis or chronic active hepatitis. Candidiasis, however, is usually the first symptom. Mutations in the AIRE gene are found in almost all patients with 2 of the 3 major signs.

APECED is more common in certain populations, such as in the Finnish population (1 in 25,000), the Sardinians (1 in 14,000) and the Iraqi Jews (1 in 9,000). The AIRE gene comprises 14 exons and is predominantly expressed in tissues that are crucial for the maturation of the immune system, such as the thymus, lymph nodes and fetal liver. Certain mutations occur more frequently in specific populations: Almost 90% of all Finnish patients carry the mutation R257X.