Abstract: Background: Historically, infectious diseases have been the primary focus of pediatric gastrointestinal disorders. However, in recent years, the diagnosis rate of genetic metabolic diseases has gradually increased. Objective: To summarize the clinical phenotypes and genotypes of common genetic metabolic diseases affecting the digestive system. Design: Case series report. Methods: This study included children who presented with gastrointestinal symptoms and had abnormal whole-exome sequencing results at a single center between January 1, 2015, and December 31, 2019. Demographic data, clinical information, and genetic testing results were extracted from the medical records system. Main outcome measures: Clinical phenotypes and genotypes. Results: Among the 320 children who underwent genetic testing in the gastroenterology department, 111 (34.7%) had abnormal results. The mean age at diagnosis was 2.4±2.8 years, and 68 (61.3%) were male. The main disease phenotypes included hereditary liver diseases in 70 cases (63.1%), with Wilson's disease and glycogen storage diseases each accounting for 15 cases, Citrin deficiency for 13 cases, Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), and bilirubin metabolism disorders for 9 cases each. Other conditions included very early-onset inflammatory bowel disease (VEO-IBD) in 8 cases (7.2%) and progressive muscular dystrophy in 10 cases (9.1%).Wilson's disease commonly presented as asymptomatic persistent transaminase elevation (53.3%), with the ATP7B gene c.2333G>T (p.R778L) being the most common mutation site (53.3%). Glycogen storage disease patients mainly exhibited hypoglycemia, hepatomegaly, abnormal liver function (93.3% for all), and elevated triglycerides (60.0%). Subtypes included type Ⅸa (6 cases), type Ⅲ (5 cases), and one case each of GSD Ⅰa, GSD Ⅱ, GSD Ⅵ, and GSD ⅩⅤ. Alagille syndrome was associated with abnormal liver function in all 9 cases, and 8 (88.9%) visited the hospital due to yellowish discolouration of the skin and sclera. The JAG1 gene mutation (Alagille syndrome type 1) was found in 8 cases (88.9%), and the NOTCH2 gene mutation (Alagille syndrome type 2) was found in 1 case. Citrin deficiency patients were mostly admitted due to yellowish discolouration of the skin and mucous membrane (92.3%) and exhibited abnormal liver enzymes, cholestasis, and hypoglycemia. All 13 cases had mutations in the SLC25A13 gene, with c.851_854del (38.5%) and c.852_855del (30.8%) being the most common mutations. Progressive familial intrahepatic cholestasis (PFIC) was characterized by hepatomegaly, elevated ALT, AST, and total bile acids in all 9 cases. The subtypes included type 2 (6 cases with ABCB11 gene mutations), type 3 (2 cases with ABCB4 gene mutations), and type 1 (1 case with ATP8B1 gene mutation). Bilirubin metabolism disorders were identified in 9 cases presenting with jaundice and/or abnormal liver function, all of which had UGT1A1 gene mutations. The most common mutation sites were c.211G>A (p.G71R) (66.7%) and A(AT)6TAAinsTA (55.6%). VEO-IBD was primarily characterized by chronic diarrhea in all 8 cases, with elevated WBC counts and CRP levels. Endoscopic findings showed cobblestone-like changes and deep ulcers in the colonic mucosa. Seven cases had IL10-RA gene mutations, with c.301C>T (p.R101W) (62.5%) and c.537G>A (p.T179T) (50%) being the most common, and one case had a heterozygous mutation in the IL10-RB gene. Conclusion: Genetic testing plays a crucial role in the diagnosis and treatment of genetic metabolic diseases affecting the digestive system in children.

Key words: Gastroenterology, Genetics, Pediatrics, Bilirubin