Monogenic inflammatory bowel disease with STXBP2 mutations is not resolved by hematopoietic stem cell transplantation but can be alleviated via immunosuppressive drug therapy

STXBP2, encoding syntaxin-binding protein 2, is involved in intracellular organelle trafficking and is associated with familial hemophagocytic lymphohistiocytosis type 5. Although STXBP2 mutations reportedly cause monogenic inflammatory bowel disease, the clinical course and underlying pathogenic mechanisms remain unclear. We identified a novel mutation in STXBP2 [c.1197delC, p.Ala400fs] in a boy with congenital intractable diarrhea and hemophagocytic lymphohistiocytosis (HLH). HLH was treated with intravenous prednisolone, cyclosporine, and dexamethasone palmitate. Hematopoietic stem cell transplantation (HSCT) along with prophylaxis for graft-versus-host-disease was performed at 5 months of age. Additionally, colonoscopies done before and after HSCT showed mild colitis with cryptitis. The patient showed elevated fecal calprotectin levels and persistent diarrhea even after HSCT and required partial parenteral nutrition. While anti-inflammatory treatment reduced diarrhea, it was not completely normalized even after HSCT, suggesting that the pathogenesis of inflammatory bowel disease associated with STXBP2 mutations involves both hyperinflammation and functional epithelial barrier defects. •A novel mutation in STXBP2 was found in an infant with HLH and VEO-IBD.•IBD and MVID were considered the cause of intractable diarrhea in the infant.•Infant's diarrhea improved with prednisone or other anti-inflammatory treatments.•Hematopoietic stem cell transplantation cured HLH, but diarrhea was persistent.•Functional epithelial barrier defects and hyperinflammation could have caused IBD.