Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea

J Crohns Colitis. 2021 Oct 7;15(10):1679-1685. doi: 10.1093/ecco-jcc/jjab056.

Abstract

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.

Keywords: Crohn’s disease; SLC26A3; congenital chloride diarrhoea; monogenic disease; ulcerative colitis.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chloride-Bicarbonate Antiporters / genetics
  • Cohort Studies
  • Diarrhea / congenital*
  • Diarrhea / epidemiology
  • Diarrhea / genetics
  • Europe / epidemiology
  • Female
  • Humans
  • Inflammatory Bowel Diseases / epidemiology*
  • Male
  • Metabolism, Inborn Errors / epidemiology*
  • Metabolism, Inborn Errors / genetics
  • Mutation
  • Prevalence
  • Sulfate Transporters / genetics
  • Young Adult

Substances

  • Chloride-Bicarbonate Antiporters
  • SLC26A3 protein, human
  • Sulfate Transporters

Supplementary concepts

  • Congenital chloride diarrhea