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INTRODUCTION: 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 diarrhea 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). Prevalence of IBD in our cohort of CLD is higher than the highest prevalence of IBD in Europe (p < 0.0001). The age of onset was variable (13.5 years, IQR: 8.5 - 23.5 years). Patients with CLD and IBD had lower z-score for height than those without IBD. 4/12 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 immunosuppressant (azathioprine or mercaptopurine), one on 5-ASA and one off-treatment. CONCLUSIONS: A substantial proportion of patients with CLD develop IBD. This suggests potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.

Original publication




Journal article


J Crohns Colitis

Publication Date



Crohn’s disease, SLC26A3, congenital chloride diarrhea, monogenic disease, ulcerative colitis