Autoimmune polyendocrinopathy [13 genes]

Autoimmune polyendocrinopathies correspond to a group of endocrine disorders caused by an abnormal immune response against the endocrine glandular tissue due to abnormalities in regulatory mechanisms. Failures in T cell self-tolerance processes (usually loss of regulatory T cell function) could prevent the apoptosis of autoreactive T cells and cause their release to the circulatory stream. In addition to immune dysregulation, polyendocrinopathy, and X-linked enteropathy syndrome (IPEX) caused by pathogenic variants in FOXP3 and autoimmune polyendocrine syndrome (APS1) caused by pathogenic variants in AIRE, other diseases could be similar and are caused by defects in genes that control the processes associated with regulatory T lymphocytes.

~1/100,000

• Diagnosis and genetic counseling
• Hematopoietic stem cell transplantation (HSCT)
• Immunosuppressants

The identification of a pathogenic variant in the genes of the panel allows for a precise molecular diagnosis, in addition to providing genetic advice. Additionally, positive genetic testing can help direct patient management and evaluate treatment options.

When there is a suspicion of an autoimmune disease with polyglandular involvement, it is recommended to perform a genetic study of the genes mainly associated with this pathology, which include AIRE, FOXP3, CTLA4, STAT1, STAT3 and other differential diagnosis genes that present overlap with autoimmune polyendocrinopathy. Although the typical presentation associated with these genes meets a series of diagnostic and disease classification criteria, sometimes these types of diseases present with a clinical presentation of variable expression that makes their recognition difficult and varies according to the age range of the patient. On the other hand, in some cases, such as the AIRE gene, the dominant forms are milder than the recessive forms, so there may be dose-dependent disorders.

• Diabetes mellitus
• Addison’s disease
• Thyroiditis
• Hepatitis
• Diarrhea