关键词: 新生儿, 遗传代谢病, 消化系统症状, 黄疸, 高通量测序, 基因突变

Abstract:

Objective To summarize the clinical phenotypes and genotypes of inherited metabolic diseases in neonates presenting with gastrointestinal symptoms. Methods A retrospective review was conducted of clinical data from children admitted to the Department of Neonatology of the First Affiliated Hospital of Henan Medical University and the Department of Neonatology of Gushi County Maternal and Child Health Hospital from November 2017 to November 2025. The included children presented with gastrointestinal symptoms as the initial manifestation, were initially suspected of having inherited metabolic diseases, and underwent genetic testing. Collected data included sex, age, clinical phenotype, and genetic testing results. Results Among the 429 children included, 196 had abnormal genetic results, yielding a positive rate of 45.69%; 105 were male and 91 were female. The main clinical manifestations were jaundice in 84.19%, cholestasis in 10.71%, feeding difficulty in 5.61%, hepatomegaly in 2.55%, vomiting in 2.04%, and diarrhea in 0.51%. The major disease phenotypes were as follows: ①Hereditary non-hemolytic unconjugated hyperbilirubinemia in 139 cases (37 with Gilbert syndrome and 102 with Crigler-Najjar syndrome type II), with clinical manifestations of jaundice and elevated unconjugated bilirubin. Eighteen UGT1A1 mutation types were identified, and the top five mutations were c.211G>A, c.1091C>T, c.-41_-40dup, c.-3275T>G, and c.1456T>G, accounting for 92.20% of all mutations. ②Sodium taurocholate cotransporting polypeptide deficiency in 11 cases, all presenting with jaundice and delayed resolution of jaundice; c.800C>T was the most common variant, with an allelic frequency of 90.90%. ③Alagille syndrome in 9 cases, all presenting with skin and scleral jaundice; 1 case also had hepatomegaly. Among them, 4 cases had type I JAG1 mutations and 5 cases had type Ⅱ NOTCH2 mutations. ④Citrin deficiency-associated neonatal intrahepatic cholestasis in 7 cases, with 2 frameshift mutations detected, c.852_855del and c.1638_1660dup, accounting for allelic frequencies of 71.43% and 28.57%, respectively. ⑤Ornithine transcarbamylase deficiency in 6 cases, all with heterozygous OTC mutations, mainly presenting with feeding difficulty and hyperammonemia; 2 cases also had jaundice and 1 had marked hepatomegaly, and the prognosis was poor in all cases. ⑥Glucose-6-phosphate dehydrogenase deficiency in 5 cases, all presenting with skin and scleral jaundice and hemolytic manifestations; all were hemizygous G6PD mutations in male infants. ⑦Very long-chain acyl-CoA dehydrogenase deficiency in 3 cases, all with homozygous ACADVL mutations and mainly presenting with vomiting and feeding difficulty. The mutations c.1843C>T (2 cases) and c.1078-1G>A (1 case) were identified. ⑧Cystic fibrosis in 3 cases, mostly presenting with jaundice and cholestasis, all compound heterozygous CFTR mutations. ⑨Wilson disease in 3 cases, all presenting with jaundice and compound heterozygous ATP7B mutations. ⑩Microvillus inclusion disease in 2 cases, both with compound heterozygous MYO5B mutations. 11Hereditary spherocytosis in 8 cases, all initially presenting with recurrent severe jaundice, mostly accompanied by severe anemia. These included 1 case of type 1 hereditary spherocytosis (ANK1), 2 cases of type 2 (SPTB), 1 case of type 3 (SPTA1), 2 cases of type 4 (SLC4A1), 1 case of type 5 (SLC4A1), and 1 case of type 1 combined with type 5 (EPB42). 12One case of Dubin-Johnson syndrome combined with Gilbert syndrome, presenting with jaundice and an ABCC2 heterozygous mutation. 13One case of Rotor syndrome, presenting with jaundice and elevated direct bilirubin, with compound heterozygous SLCO1B3 mutations. 14One case of galactosemia, with compound heterozygous GALT mutations. 15One case of citrullinemia type I, presenting with feeding difficulty and hepatomegaly, with compound heterozygous ASS1 mutations.16 One case of congenital bile acid synthesis disorder type 3, presenting with jaundice, elevated liver enzymes, and cholestasis, with a homozygous CYP7B1 mutation. 17One case of progressive familial intrahepatic cholestasis type 1, with compound heterozygous ATP8B1 mutations. 18One case of very early-onset inflammatory bowel disease combined with Gilbert syndrome, with vomiting, diarrhea, feeding difficulty, and decreased bowel sounds as the main manifestations, and a heterozygous mutation at PLGC2 c.3670C>T. Conclusion This study confirms the high diagnostic value of genetic testing in neonates presenting with gastrointestinal symptoms. It systematically elucidates the disease spectrum and mutation characteristics of inherited metabolic diseases in this population, providing important data support for the development of efficient clinical diagnostic pathways, individualized treatment, and genetic counseling.

Key words: neonate, inherited metabolic disorders, digestive system symptoms, jaundice, high-throughput sequencing, gene mutation