CYP7B1基因变异致先天性胆汁酸合成障碍3型2例并文献复习  

Congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variation in 2 cases and literature review

作　　者：王彩红 陆妹 赵静 黄冰清 叶萍萍 王建设 Wang Caihong;Lu Mei;Zhao Jing;Huang Bingqing;Ye Pingping;Wang Jianshe(Department of Infectious Diseases,Xiamen Children′s Hospital,Children′s Hospital of Fudan University at Xiamen,Xiamen 361006,China;Department of Pediatrics,Women and Children′s Hospital,School of Medicine,Xiamen University,Xiamen 361003,China;Department of Infectious Diseases,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院厦门医院(厦门市儿童医院)感染科,厦门361006 [2]厦门大学附属妇女儿童医院,厦门市妇幼保健院儿内科,厦门361003 [3]国家儿童医学中心,复旦大学附属儿科医院感染传染科,上海201102

出　　处：《中华儿科杂志》2024年第9期877-882,共6页Chinese Journal of Pediatrics

摘　　要：目的总结CYP7B1基因变异致先天性胆汁酸合成障碍3型患儿的临床表型和遗传学特点。方法病例系列研究,回顾性分析2021年1月至2023年12月复旦大学附属儿科医院厦门医院感染科和厦门大学附属妇女儿童医院儿内科诊治的2例因CYP7B1基因变异致BASD3的临床资料和遗传学检测结果。并分别以“先天性胆汁酸合成障碍3型”“氧固醇7α-羟化酶”“BASD3”“Oxysterol 7α-Hydroxylase Deficiency”“Oxysterol 7α-Hydroxylase Gene”“CYP7B1 liver”为关键词检索中国知网、万方数据库和PubMed数据库自建库至2023年12月的中英文文献。对CYP7B1基因变异致BASD3患儿的主要临床表现和基因型特点进行描述和总结。结果2例BASD3患儿中男女各1例,就诊年龄分别为3月龄18日龄和2月龄7日龄,均以新生儿胆汁淤积症伴肝大就诊。生化提示高直接胆红素血症,转氨酶升高,但γ-谷氨酰转移酶(GGT)和总胆汁酸正常或基本正常。例1为CYP7B1基因c.525-526insCAAGTTGG(p.Asp176GInfs*15)和c.334C>T(p.Arg112Ter)复合杂合变异,经口服鹅脱氧胆酸治疗黄疸消退,肝功能恢复正常;例2为CYP7B1基因c.334C>T(p.Arg112Ter)纯合,确诊时已发生肝衰竭,口服鹅脱氧胆酸无效,因腹部增强CT提示血管源性肿瘤行亲体肝移植。文献复习符合检索条件英文文献9篇、无中文文献报道。包括本研究2例共报道12例患儿,男9例、女3例。所有BASD3患儿均在婴幼儿期起病,主要表现为黄疸、肝大和(或)脾大,部分伴有肝硬化、肝衰竭、肾肿大、低血糖、自发性出血。伴多囊肾5例。CYP7B1基因c.334C>T(p.Arg112Ter)为最常见变异,纯合4例,复合杂合2例。12例患儿中,口服鹅去氧胆酸治疗6例,自体肝存活4例;6例未用鹅去氧胆酸治疗,均肝移植或死亡。结论BASD3是一种罕见的遗传性胆汁淤积症,结合胆红素和转氨酶明显升高,而GGT和总胆汁酸正常可作为诊断线索。c.334C>T是CYP7B1基因常见致病�Objective To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3(BASD3)disorder caused by CYP7B1 gene variation.Methods This was a case series study.Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases,Children′s Hospital of Fudan University at Xiamen and Department of Pediatrics,Women and Children′s Hospital,School of Medicine,Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed.Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure(CNKI),Wanfang Data and PubMed with the combined keywords of"Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3"and"CYP7B1 liver"both in Chinese and English.The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized.Results Two BASD3 patients,1 male and 1 female,were admitted at the ages of 3 months and 18 days,and 2 months and 7 days,respectively.Both patients presented with neonatal cholestasis and hepatomegaly.Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels,while gamma-glutamyltransferase(GGT)and total bile acid levels were normal or nearly normal.Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15)and c.334C>T(p.Arg112Ter).Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid(CDCA).Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter)in CYP7B1 gene.Patient 2 was in liver failure status already and not reactive to oral CDCA administration.Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin.Literature review revealed no cases of BASD3 re

关 键 词：胆汁淤积 胆汁酸合成障碍 氧化固醇7α-羟化酶 基因 CYP7B1 

分 类 号：R725.7[医药卫生—儿科]