P186 Comparative Analysis of Clinical Phenotypes and Pathogenic Features between Late-Onset and Infantile-Onset Monogenic Inflammatory Bowel Disease

Abstract

Abstract Background Previous research on monogenic IBD (m-IBD) has mainly focused on very-early-onset IBD (VEO-IBD) and Montreal classification A1 type IBD patients. In non-A1 type (age > 16y) late-onset IBD patients, some individuals also exhibit IBD manifestations due to monogenic mutations. Here we systematically review the literature, using infantile-onset monogenic IBD patients as a control, to explore the genetic characteristics, clinical presentations, and treatment strategies of late-onset monogenic IBD. Methods Based on the onset age of IBD, m-IBD was categorized into infantile-onset (IO, <2 years) and late-onset (LO, >16 years as non-A1 type based on Montreal classification) groups. A systematic review was conducted to analyze the gastrointestinal (GI) clinical features of detailed cases published from January 1990 to June 2023 and to summarize the correlation between genetic pathogenesis and onset ages. Results 512 m-IBD cases (398 IO and 114 LO) associated with 87 genes were included. Of these genes, 25 out of 87 genes were found to cause both IO and LO conditions. Crohn’s disease (CD) was the predominant type of IBD, account for 42.2% of IO and 44.7% of LO cases. Difficult-to-treat IBD patients showed similar rates (17.4% for IO and 13.0% for LO). However, infantile-onset cases were predominantly associated with complex perianal disease (13.5%), while late-onset cases were linked to postoperative recurrence following surgical resections (10.6%). Anti-inflammatory medicine and biologics were the main strategies, but in infantile-onset (IO) cases, immunosuppressants (57.9%), parenteral nutrition (26.8%), gastroenterostomy (20.2%), and HSCT (24.6%) were more frequently utilized compared to late-onset (LO) cases, where intestinal resection (37.8%) was more prevalent. Homozygosity was the predominant zygosity type (39.9% in IO and 39.3% in LO), while heterozygosity was more prevalent in LO cases (28.9%) compared to IO cases (13.3%) (p<0.05). Most of the genes associated with median onset ages of IBD before 2 years were causative genes for primary immunodeficiency (PID), whereas significantly lower rate of PID genes mutation was found in LO cases (26/27, 96.3% vs. 6/11, 54.5%, p= 0.005). Conclusion m-IBD patients predominantly present with CD, ulceration and atypical pathology, colon involvement, and difficult to treat regardless of onset ages, but vary in terms of family history, GI symptoms, location of the lesion, polyps and villous atrophy, type of complications, treatment options, and type of Difficult-to- treat IBD.