Phenotypic and genotypic characterization of inflammatory bowel disease in children under six years of age in China

Abstract

AIMTo analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease (VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing.METHODSA retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing.RESULTSA total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn’s disease (CD) or CD-like intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients (16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo (interquartile range (IQR): 4 to 78) and 43.5 mo (IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group (P = 0.001). However, there were no significant differences between weight-for-age and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency.CONCLUSIONA high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.

Special clinical characteristics and outcomes in Chinese pediatric patients with early‐onset Crohn's disease

“…In our study, patients with EO‐CD, especially with VEO‐CD, had lower remission rates but higher mortality rates than those with LO‐CD. There are limited studies on mortality in patients with PIBD . We found that the Chinese group had a higher mortality rate than the western European group.…”

“…There are limited studies on mortality in patients with PIBD. 11,13,31,32 We found that the Chinese group had a higher mortality rate than the western European group. One pediatric study has focused on mortality in patients diagnosed at childhood with CD.…”

“…During the median follow‐up of 11 years, five deaths were reported among 538 patients with childhood‐onset CD, of which only two (0.4%) deaths were CD‐related. Another Chinese study also showed a high mortality rate in VEO‐IBD patients …”

“…Another Chinese study also showed a high mortality rate in VEO-IBD patients. 32 Previous studies have reported that children diagnosed with CD have lower body weight than a healthy reference population. Growth retardation at the time of diagnosis was found in 9% to 24% of the patients, and malnutrition was found in 10% to 57%.…”

Current global trends in the incidence of pediatric-onset inflammatory bowel disease

“…The incidence of IBD in industrialized countries is higher than that in developing countries; however, overwhelming data suggest that its prevalence is increasing worldwide in both adult[ 3 ] and pediatric populations[ 4 ] and that its distribution is uneven among regions[ 5 ]. Many explanations have been proposed, but the hypothesis that exposure to environmental and genetic factors is a fundamental contributor to the development of IBD has been challenged by several new observations[ 6 - 10 ]. Whether the etiology of pediatric-onset IBD differs from that of adult-onset IBD remains unknown[ 11 ].…”