Clinical Heterogeneity of Immune Dysregulation, Polyendocrinopathy, Enteropathy, X‐Linked Syndrome: A French Multicenter Retrospective Study. Issue 10 (October 2018)

• Record Type: Journal Article
• Authors: Duclaux‐Loras, R.; Charbit‐Henrion, F.; Neven, B.; Nowak, J.; Collardeau‐Frachon, S.; Malcus, C.; Ray, P. F.; Moshous, D.; Beltrand, J.; Goulet, O.; Cerf‐Bensussan, N.; Lachaux, A.; Rieux‐Laucat, F.; Ruemmele, F. M.
• Is Part Of: Clinical and translational gastroenterology. Volume 9:Issue 10(2018)
• Publication Date: 2018-10
• Subjects: Stomach -- Diseases -- Periodicals; Intestines -- Diseases -- Periodicals; Gastroenterology; Gastrointestinal Diseases; Liver Diseases; Intestines -- Diseases; Stomach -- Diseases; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; 616.33
• DOI: 10.1038/s41424-018-0064-x
• Languages: English
• ISSNs: 2155-384X

Abstract

Abstract : Objective: : Immune dysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome is an autoimmune disease caused by mutations in the forkhead box protein 3 gene ( FOXP3 ), which encodes a key regulator of immune tolerance. The aim of this study was to describe the clinical heterogeneity of the disease in a national French cohort. Methods: : Multicenter retrospective study of patients diagnosed with IPEX syndrome caused by mutations in FOXP3 . Results: : Thirty children from 26 families were included. Age at disease onset (median [first to third quartile]) was 1.5 mo [0–84] and at death 3.5 years [0–10.5] ( n = 15) indicating a high heterogeneity. Initial presentation was diarrhoea (68%), type 1 diabetes (T1D; 25%), skin lesions (7%) and nephropathy (3%). During the course of the disease the following main symptoms were observed: diarrhoea (100%), skin lesions (85%), T1DM (50%), severe food allergies (39%), haematological disorders (28%), nephropathies (25%), hepatitis (14%) as well as the presence of a variety of autoantibodies. Immunosuppressive mono‐ or combination therapy led to improvement in eight children. Three boys displayed a stable disease course without any immunosuppressive medication. Overall 10‐year survival rate was 43% (42% in transplanted patients and 52% in patients on immunosuppressive therapy). Five out of 22 identified FOXP3 mutations have not been described yet: c.‐23 + 1G > A, c.‐23 + 5G > A, c.264delC, c.1015C > T and c.1091A > G. The first two produced atypical, attenuated phenotypes. Missense and frameshift mutations affecting the forkhead domain were associated with poor survival (Gehan‐Wilcoxon p = 0.002). Conclusion: : The broad phenotypic heterogeneity of IPEX raises questions about modifying factors and justifies early FOXP3 sequencing in suspected cases.