Analysis of clinical features and genotype of 48 infantile-onset inflammatory bowel disease / 中华实用儿科临床杂志

ABSTRACT

Objective:To summarize clinical and genetic features of infantile-onset inflammatory bowel disease(IO-IBD) patients.Methods:The clinical data of 48 IO-IBD patients from Beijing Children′s Hospital, Capital Medical University, including age of onset, family history, clinical manifestations and drug efficacy were retrospectively analyzed.Based on target gene panel, next generation sequencing (NGS) was performed for 43 patients, and further compared clinical features between gene mutation and non-gene mutation IO-IBD groups.Results:Among the 48 IO-IBD patients, 41 cases suffered from Crohn′s disease (CD) and 7 cases were ulcerative colitis (UC). The median age of onset was 2.00(0.24-6.00) months, and 45.8%(22/48 cases) of patients′ onset age was within 1 month.Diarrhea (48/48 cases, 100%), fever (45/48 cases, 93.8%) and hematochezia (37/48 cases, 77.1%) were the main clinical symptoms.Perianal lesions and rashes were common extraintestinal manifestations, accounting for 43.8%(21/48 cases) each.Among 41 CD patients, 73.2%(30/41 cases) had predominantly colonic disease (L2 type), and disease behavior was mainly nonstricturing and nonpenetrating (B1 type) (33/41 cases, 80.5%). Among 7 UC patients, 57.1%(4/7 cases) had predominantly pancolonic (E4 type). The surgical rate of the 48 IO-IBD patients was 12.5%(6/48 cases), the clinical remission rate was 50.0%(24/48 cases), and the mortality rate was 25.0%(12/48 cases). Among the 43 IO-IBD patients, 23 (23/43 cases, 53.5%) had meaningful gene mutations, of which 22 cases had mutations in interleukin-10 receptor A ( IL-10 RA) and 1 case with mutation in TTC37.A total of 11 mutation sites were detected in 22 patients with IL-10 RA mutations, including one novel mutation site c. 635G>C (p.R212P); 19 cases c. 301C>T (p.R101W) and 8 cases c. 537G>A (p.T179T) that were common mutation sites.Compared with non-gene mutation IO-IBD group, patients in gene mutation IO-IBD group had earlier onset age [0.3 (0.1-1.0) months vs.(6.27±5.64) months, P<0.001], higher proportion of malnutrition [14 cases(60.9%) vs.5 cases(25.0%), P=0.018], oral ulcers [14 cases(60.9%) vs. 30 cases(15.0%), P=0.006] and perianal lesions [17 cases(73.9%) vs.3 cases(15.0%), P<0.001], and the lower rate of clinical remission[7 cases(30.4%) vs.15 cases(75.0%), P=0.004]. Conclusions:IO-IBD patients had a high rate of monogenic mutation, and IL-10 RA gene mutation was the common mutation.IO-IBD patients developing with gene mutation were characterized by early age of onset, higher incidence of malnutrition, oral ulcers, perianal lesions, and the lower clinical remission rate.