This rare disorder results from mutation of the transcriptional activator gene, FOXP3, which causes regulatory T-cell dysfunction and a subsequent autoimmune disorder Autoimmune Disorders In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following types of hypersensitivity reactions may be involved: Type II: Antibody-coated... read more (1 General reference IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) is an X-linked recessive syndrome involving aggressive autoimmunity. This rare disorder results from mutation of the transcriptional... read more ).
IPEX syndrome manifests as severe enlargement of the secondary lymphoid organs, type 1 diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , eczema Atopic Dermatitis (Eczema) Atopic dermatitis is a chronic relapsing inflammatory skin disorder with a complex pathogenesis involving genetic susceptibility, immunologic and epidermal barrier dysfunction, and environmental... read more , food allergies Food Allergy Food allergy is an exaggerated immune response to dietary components, usually proteins. Manifestations vary widely and can include atopic dermatitis, gastrointestinal or respiratory symptoms... read more , and infections. Secondary enteropathy leads to persistent diarrhea and failure to thrive.
Diagnosis of IPEX syndrome is suggested by clinical features and confirmed by genetic analysis. Genetic counseling and targeted genetic testing for siblings and offspring should be considered.
1. Chen CB, Tahboub F, Plesec T, et al: A review of autoimmune enteropathy and its associated syndromes. Dig Dis Sci 65(11): 3079–3090, 2020. doi: 10.1007/s10620-020-06540-8
Treatment of IPEX Syndrome
Hematopoietic stem cell transplantation
Untreated, IPEX syndrome is usually fatal in the first year of life. Hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more has been shown to be beneficial with some resolution of autoimmune disease and decreased development of additional autoimmune manifestations. Long-term follow-up of patients with IPEX syndrome treated with hematopoietic stem cell transplantation continues (1 Treatment reference IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) is an X-linked recessive syndrome involving aggressive autoimmunity. This rare disorder results from mutation of the transcriptional... read more ).
Barzaghi F, Amaya Hernandez LC, Neven B, et al: Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study. J Allergy Clin Immunol 141(3):1036–1049.e5, 2018. doi: 10.1016/j.jaci.2017.10.041