P755 Congenital chloride diarrhoea and inflammatory bowel disease: an emerging association

Abstract

Background Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by the mutation in member 3 of the solute carrier 26 (SLC26A3). The phenotypic expression is a life-long severe watery Chloride rich diarrhea. Anecdotal association with inflammatory bowel disease (IBD) has been reported suggesting that underlying molecular mechanisms could represent part of an evolving association between IBD and channelopathies. We aimed to investigate this association in a cohort of CLD pediatric patients. Methods A European-based call for cases was made in CLD patients followed up in five different countries. A case report form for each patient was then completed. Results A total of 74 patients with CLD with a range of different CLD mutations were enrolled in the study. Twelve patients of 64 (16%) demonstrated colonic inflammation and were finally diagnosed with IBD: 8 patients with Crohn’s Disease, 2 with Ulcerative Colitis, and 2 IBD-like colitis (IBD-U). The diagnosis was made at a median of 12 years old (IQR: 6–30). Patients had different ethnicities (7 European, 2 Middle East, 1 North Africa, 1 Pakistan, 1 Central Africa). Among the 12 IBD, 2 had a 5-ASA-based treatment, 3 required immunosuppressant and 6 had biologics (Infliximab, Adalimumab and Vedolizumab). Three patients underwent surgery for ileostomy formation for CD that was non-responsive to multiple line of biologics (anti-TNF and anti-integrin): one had colectomy the remnant two colon preservation. Clinical characteristics, such as premature delivery, low weight at birth, fecal Cl- at diagnosis and amount of Cl- supplementation (mmol/kg) did not differ between patients with or without IBD. All patients underwent genotyping for CLD diagnosis and we did not find any specific genetic mutation linked to the development of IBD. Conclusion Sixteen percent of patients enrolled with CLD in our cohort developed IBD. Despite different presentations (CD, UC, IBD-U) all patients had colonic without ileal/small bowel involvement, in line with preliminary murine models of CLD demonstrating a role of colonic mucous layer in the development of colonic inflammation (Xiao et al Acta Physiol Oxf Engl 2014; 211:161–175). Patients’ IBD treatment included a wide range with variable success. Patients with IBD did not differ in their clinical characteristics or genetic mutations compared with non-IBD CLD patients. The role of genetic variants outside the CLD-gene and the microbiome in this association are under investigation.

Prenatal biochemical diagnosis of two forms of congenital diarrheal disorders (congenital chloride diarrhea and congenital sodium diarrhea): A series of 12 cases

“…They responded more or less to treatment and some required surgery. No clinical or genetic difference has been shown with those who have not developed IBD 17 . In our series, one patient developed IBD, but he was SCD‐affected.…”

Rare complication of inflammatory bowel disease-like colitis from glycogen storage disease type 1b and its surgical management: A case report

“…The patient underwent allogenic stem cell transplantation and saw significant improvement in obstructive symptoms and biochemical parameters. Norsa et al [ 19 ] described a rare cause of IBD-like colitis, which is congenital chloride diarrhoea, a rare autosomal recessive disease secondary to SLC26A3 gene mutation. Among the twelve patients with IBD or IBD-like colitis, two were treated with 5-aminosalicylate acid, three with immunosuppressants and six with biologics.…”