Characteristics of monogenic inflammatory bowel disease in very early-onset cases: a Japanese multicenter registry study

Background/Aims: Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed before 6 years of age, is highly influenced by genetic factors. Monogenic IBD is a type of enterocolitis caused by a single pathogenic variant. However, information on Asian patients with VEO-IBD and monogenic IBD is limited. This study investigated real-world data on VEOIBD and monogenic IBD in Japan. Methods: We evaluated patients with VEO-IBD registered in the Japanese Pediatric Inflammatory Bowel Disease Registry, a multicenter prospective registry study conducted between 2012 and 2021. We categorized patients into monogenic and non-monogenic IBD groups and compared their clinical characteristics and outcomes. Results: Among 703 pediatric patients with IBD, 68 (9.7%) had VEO-IBD. Of these, 26 (38.2%) had ulcerative colitis, 16 (23.5%) had Crohn's disease, 23 (33.8%) had unclassified IBD (IBD-U), and 3 (4.4%) had Behçet's disease. Genetic testing was performed in 25 patients (36.8%), and monogenic IBD was identified in 5 of the 23 patients with IBD-U (7.4% of the VEO-IBD cohort). All 5 monogenic cases presented with an IBD-U phenotype. Monogenic IBD included A20 haploinsufficiency, interleukin-10 receptor subunit alpha deficiency, chronic granulomatous disease, Wiskott-Aldrich syndrome, and Hermansky-Pudlak syndrome. Monogenic IBD was significantly associated with IBD-U phenotype (P= 0.015) and severe infections before 1 year of age (P= 0.004). Conclusions: Patients with VEO-IBD who present an IBD-U phenotype and have a history of severe infections during infancy should be prioritized for genetic analysis to investigate the possibility of monogenic IBD.