Autoimmune polyendocrine syndrome

Autoimmune polyendocrine syndromes (APSs) are a group of rare, varied conditions where the immune system attacks more than one endocrine organ, though non-endocrine organs may also be involved. Three main types exist, along with other diseases that feature endocrine autoimmunity.

Type 1 is caused by a recessive mutation in the AIRE gene, leading to issues like hypoparathyroidism, adrenal insufficiency, hypogonadism, vitiligo, and candidiasis. Type 2 follows an autosomal dominant pattern with multiple genes involved, resulting in adrenal insufficiency paired with hypothyroidism or type 1 diabetes. IPEX syndrome is X-linked recessive, caused by a FOXP3 gene mutation on the X chromosome; most affected boys develop diabetes and diarrhea, and many die from widespread autoimmune attacks, while girls are carriers who may experience mild symptoms.

Each type has a distinct genetic cause. In IPEX syndrome, the FOXP3 gene (located at Xp11.23) is responsible for the condition, inherited via an X-linked recessive pattern in males.

For diagnosing type 1, methods include endoscopic exams, CT scans, and histologic testing. Differential diagnoses for this condition include CD25 deficiency, STAT5B deficiency, severe combined immunodeficiency, and X-linked thrombocytopenia.

Management may involve immunosuppressive therapy for type 1, and ketoconazole can be used in certain circumstances for this type as well.