| المساهمون: |
Norsa, Lorenzo, Berni Canani, Roberto, Duclaux-Loras, Remi, Bequet, Emeline, Köglmeier, Jutta, Russell, Richard K, Uhlig, Holm H, Travis, Simon, Hollis, Jennifer, Koletzko, Sibylle, Grimaldi, Giusi, Castaldo, Giuseppe, Rodrigues, Astor, Deflandre, Jaque, Dembinski, Lukasz, Shah, Neil, Heinz-Erian, Peter, Janecke, Andrea, Leskinen, Saara, Wedenoja, Satu, Koskela, Ritva, Lachaux, Alain, Kolho, Kaija-Leena, Ruemmele, Frank M, HUS Gynecology and Obstetrics, University of Helsinki, Department of Obstetrics and Gynecology, Clinicum, Children's Hospital, HUS Children and Adolescents |
| الوصف: |
Background Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice. Methods We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD. Results In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn’s disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5–23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment. Conclusions A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer. |
