Crohn-like Disease Affecting Small Bowel Due to Monogenic SLCO2A1 Mutations: First Cases of Chronic Enteropathy Associated with SLCO2A1 Gene [CEAS] in France

Abstract

Introduction: Multiple chronic ulcers of small intestine are mainly ascribed to Crohn's disease. Among possible differential diagnoses are chronic ulcers of small bowel caused by abnormal activation of the prostaglandin pathway either in the archetypal but uncommon non-steroidal anti-inflammatory drug [NSAID]-induced enteropathy, or in rare monogenic disorders due to PLA2G4A and SLCO2A1 mutations. SLCO2A1 variants are responsible for CEAS [chronic enteropathy associated with SLCO2A1], a syndrome which was exclusively reported in patients of Asian origin. Herein, we report the case of two French female siblings, P1 and P2, with CEAS.

Case report: P1 underwent iterative bowel resections [removing 1 m of small bowel in total] for recurrent strictures and perforations. Her sister P2 had a tight duodenal stricture which required partial duodenectomy. Next-generation sequencing was performed on P1's DNA and identified two compound heterozygous variants in exon 12 in SLCO2A1, which were also present in P2.

Conclusion: CEAS can be detected within the European population and raises the question of its incidence and recognition outside Asia. Presence of intractable recurrent ulcerations of the small intestine, mimicking Crohn's disease with concentric strictures, should motivate a genetic search for SLCO2A1 mutations, particularly in the context of family history or consanguinity.

Keywords: Small bowel ulcerations; crohn-like ulcers; monogenic enteropathy; prostaglandines; small bowel stricture.

Graphical Abstract

Figure 1.

Imaging, histology, and genetics of Patient 1 [P1] with chronic enteropathy associated with SLCO2A1 gene mutation [CEAS]. A: Coronal presurgical computed tomographic enterography showing a tight anastomotic stricture [arrow] with upstream dilatation of the ileal loops. B: Small bowel resection with petechial subserosa without sclerolipomatosis and multifocal short strictures alternating with saccular dilatation of the loop. C: Circular shallow ulcers delimiting each stricture [arrows] as shown after opening the ileal loops [scale mark of 2 cm]. D, E: Section through a stricture displaying superficial erosion with villous blunting and congestion limited to this area with no further lesion [haematein eosin and saffron stains] .F: Schematic representation of SLCO2A1 gene, highlighting both variants in exon 12. Each variant is localised on a different allele as shown on the IGV screenshot [Integrative Genomics Viewer, https://software.broadinstitute.org].