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IPEX Syndrome.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
2004 Oct 19 [updated 2011 Jan 27].

Excerpt

CLINICAL CHARACTERISTICS:

IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, eczematous dermatitis, and endocrinopathy (most commonly insulin-dependent diabetes mellitus). Most children have other autoimmune phenomena including Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements or sepsis; a few with a milder phenotype have survived into the second or third decade of life.

DIAGNOSIS/TESTING:

Diagnosis is based on clinical features and on the identification of a mutation in FOXP3. FOXP3 is the only gene in which mutations are known to cause IPEX syndrome. Approximately 25% of males with symptoms suggestive of IPEX syndrome have mutations identified in FOXP3.

MANAGEMENT:

Treatment of manifestations: Immunosuppressive agents (e.g., cyclosporin A, FK506) alone or in combination with steroids; sirolimus (rapamycin) for persons in whom FK506 therapy is toxic or ineffective; granulocyte colony stimulating factor (G-CSF, filgrastim) for autoimmune neutropenia; nutritional support; standard treatment of diabetes mellitus and autoimmune thyroid disease. Bone marrow transplantation (BMT) can resolve clinical symptoms. Prevention of primary manifestations: BMT, if performed early in the course of disease. Prevention of secondary complications: Prophylactic antibiotic therapy for those with autoimmune neutropenia or recurrent infections; aggressive management of dermatitis with topical steroids and anti-inflammatory agents to prevent infection. Surveillance: Periodic evaluation of complete blood count, glucose tolerance, thyroid function, kidney function, and liver function for evidence of autoimmune disease. Evaluation of relatives at risk: If the family-specific mutation is known, FOXP3 molecular genetic testing in at-risk males immediately after birth to permit early diagnosis and BMT before significant organ damage occurs; otherwise, monitoring at-risk males for symptoms to enable early diagnosis and treatment.

GENETIC COUNSELING:

IPEX syndrome is inherited in an X-linked manner. The risk to sibs of the proband depends on the carrier status of the mother. If the mother of the proband is a carrier, the chance of transmitting the disease-causing mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation are carriers and will not be affected. Affected males pass the disease-causing mutation to all of their daughters and none of their sons. Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are possible for families in which the disease-causing mutation has been identified.

Copyright © 1993-2015, University of Washington, Seattle. All rights reserved.

PMID:
20301297
[PubMed]
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