IPEX syndrome [Immune dysregulation, polyendocrinopathy, enteropathy, X-linked, OMIM#304790] is characterized by the onset in infancy due to enteropathy, type 1 diabetes mellitus, and dermatitis. Other autoimmune phenomena including Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia and tubular nephropathy are also commonly described. Without aggressive treatment (immunosuppression or hematopoietic stem cell transplantation) the majority of affected individuals die within the first two year so life.
Mutations in the FOXP3 [OMIM#300292] gene cause IPEX syndrome. FOXP3 plays an important role in the development and function of naturally occurring CD4-positive/CD25-positive T regulatory cells, which are involved in active suppression of inappropriate immune responses. Individuals with truncating mutations (nonsense, frameshift, splicing mutations) typically have severe-early onset IPEX syndrome. A number of affected individuals have been identified with missense mutations, some of which appear to be functionally hypomorphic, and are associated with a milder phenotype.