南宁地区遗传代谢性肝内胆汁淤积症患儿的临床特征及基因分析

肝脏 ›› 2022, Vol. 27 ›› Issue (10): 1123-1128.

南宁地区遗传代谢性肝内胆汁淤积症患儿的临床特征及基因分析

庞智东, 颜云盈, 徐江燕, 阙宇晨

530011 南宁广西医科大学附属南宁市妇幼保健院儿科(庞智东,颜云盈,徐江燕),检验科(阙宇晨)

收稿日期:2021-07-06 出版日期:2022-10-31 发布日期:2022-11-22
通讯作者: 颜云盈,Email:hspxh123456@sina.com
基金资助:
广西壮族自治区卫生和计划生育委员会自筹经费科研(Z20180254)

Clinical characteristics and gene analysis of infants with genetic metabolic intrahepatic cholestasis in Nanning

PANG Zhi-dong, YAN Yun-ying, XU Jiang-yan, QUE Yu-chen

Nanning Maternity And Child Health Hospital, Guangxi 530011, China

Received:2021-07-06 Online:2022-10-31 Published:2022-11-22
Contact: YAN Yun-ying, Email:hspxh123456@sina.com

摘要/Abstract

摘要： 目的探讨南宁地区遗传代谢性肝内胆汁淤积症患儿的临床特征及基因变异特征。方法以2016年1月至2020年12月接受治疗的116例在南宁地区出生的疑似遗传代谢性肝内胆汁淤积症患儿作为研究对象,收集患儿的临床资料,采用目标基因捕获结合高通量测序技术进行基因检测并采用Sanger进行验证。结果 116例患儿中,35例患儿检测到基因突变,其中SLC25A13 基因突变11例(31.43%),JAG1 基因突变8例(22.86%),ABCB11 基因突变7例(20.00%),HSD3B7 基因突变5例(14.29%),CFTR 基因和AKR1D1 基因突变各2例(5.71%)。基因突变的胆汁淤积症患儿中有希特林蛋白缺乏症11例(31.43%)、Alagille综合征8例(22.86%)、进行性家族性肝内胆汁淤积症2型7例(20.00%)、先天性胆汁酸合成障碍1型4例(11.43%)先天性胆汁酸合成障碍2型3例(8.57%)、囊性纤维化2例(5.71%)。基因突变胆汁淤积症患儿ALT水平为(244.85±70.64) U/L,高于非基因突变胆汁淤积症患儿(201.24±75.32)U/L(P<0.05),而两组患儿的性别、发病年龄、就诊年龄、体质量、喂养方式、皮肤染黄时间、白陶土色便、AST、γ-GGT、ALP、TBA、TBil、TP、Alb、Glb、肝脏彩超情况、脾脏彩超情况和胆囊彩超情况等差异均无统计学意义(P>0.05)。结论南宁地区发生基因突变的肝内胆汁淤积症患儿病因繁多,临床无显著特征,通过高通量测序技术对临床疑似遗传代谢病的肝内胆汁淤积症患儿的诊断有重要价值。

关键词: 遗传性代谢疾病, 胆汁淤积症, 儿童患者, 高通量测序技术

Abstract: Objective To investigate the clinical characteristics and gene mutation characteristics of infants with genetic metabolic intrahepatic cholestasis in Nanning. Methods A total of 116 infants with suspected genetic metabolic intrahepatic cholestasis in Nanning, who were treated in our hospital from January 2016 to December 2020, were collected as the research objects. The clinical data of all infants were collected. Target gene capture combined with high-throughput sequencing technology was used for gene detection, and Sanger was used for verification. Results (1) A total of 116 infants were included in this study, and there were 35 with gene mutation, including 11 of SLC25A13 gene mutation (31.43%), 8 of JAG1 gene mutation (22.86%), 7 of ABCB11 gene mutation (20.00%), 5 of HSD3B7 gene mutation (14.29%), 2 of CFTR gene mutation and 2 of AKR1D1 gene mutation (5.71%). (2) There were 11 of Citrin Protein deficiency (31.43%), 8 of Alagille syndrome (22.86%), 7 of progressive familial intrahepatic cholestasis of type 2 (20.00%), 4 of congenital bile acid synthesis disorder of type 1 (11.43%), 3 of congenital bile acid synthesis disorder of type 2 (8.57%), and 2 with cystic fibrosis (5.71%). (3) ALT level in infants of cholestasis with gene mutation was (244.85±70.64) U/L, which was significantly higher than those in infants of cholestasis without gene mutation (P<0.05), and there were no significant differences in gender, age of onset, age of treatment, weight, feeding pattern, yellow skin dyeing time, white earthen stool, AST, γ-GGT, ALP, TBA, TBil, TP, Alb, Glb, color Doppler ultrasound of liver, spleen and gallbladder (P>0.05). Conclusion The etiology of infants with intrahepatic cholestasis with gene mutation in Nanning is various and the clinical features are not significant. High throughput sequencing technology is of great value in the diagnosis of infants with intrahepatic cholestasis with suspected genetic metabolic diseases clinically.

Key words: Hereditary metabolic diseases, Cholestasis, Infants, High-throughput sequencing technology

庞智东, 颜云盈, 徐江燕, 阙宇晨. 南宁地区遗传代谢性肝内胆汁淤积症患儿的临床特征及基因分析[J]. 肝脏, 2022, 27(10): 1123-1128.

PANG Zhi-dong, YAN Yun-ying, XU Jiang-yan, QUE Yu-chen. Clinical characteristics and gene analysis of infants with genetic metabolic intrahepatic cholestasis in Nanning[J]. Chinese Hepatolgy, 2022, 27(10): 1123-1128.

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