先天性非溶血性黄疸的研究进展

鲁杰; 李武; 刘叶

doi:10.3969/j.issn.1001-5256.2021.01.048

先天性非溶血性黄疸的研究进展

DOI: 10.3969/j.issn.1001-5256.2021.01.048

昆明医科大学第一附属医院感染性疾病科，昆明 650032

基金项目:

云南省自然科学基金 (2009CD087);

国家十二五科技重大专项协助课题 (2012ZX10002003);

云南省科技厅-昆明医科大学联合基金重点项目 (2017FE468〔-173〕)

作者贡献声明：鲁杰负责课题设计，资料分析，撰写论文；李武负责拟定写作思路，指导撰写文章并最后定稿; 刘叶参与收集数据，修改论文。

详细信息

作者简介:
鲁杰(1994—)，女，主要从事肝纤维化的基础和临床研究

通信作者:
李武，liwukm@126.com

中图分类号: R575
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- 被引次数: 0
出版历程
- 收稿日期: 2020-06-27
- 录用日期: 2020-08-31
- 出版日期: 2021-01-20

Research advances in congenital non-hemolytic jaundice

Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

摘要

摘要: 先天性非溶血性黄疸是黄疸性疾病中的一大类，除母乳性黄疸外，临床上相对罕见，多属遗传代谢类肝病，包括以非结合性胆红素升高为主的Gilbert综合征、Crigler-Najjar综合征、Lucey-Driscoll综合征，和以结合胆红素升高为主的Dubin-Johnson综合征、Rotor综合征等。回顾近期国内外文献，主要就六种遗传性先天性非结合性黄疸的发病机制、基因特点、诊治进展及鉴别诊断进行综述。
- 黄疸 /
- 吉尔伯特病 /
- Crigler-Najjar综合征 /
- 黄疸, 慢性特发性
Abstract: Congenital non-hemolytic jaundice is an important type of jaundice diseases, and except breast milk jaundice, the other types of this disease are relatively rare in clinical practice. Most of them belong to genetic and metabolic liver diseases, including Gilbert syndrome, Crigler-Najjar syndrome, and Lucey-Driscoll syndrome with an increase in unconjugated bilirubin and Dubin-Johnson syndrome and Rotor syndrome with an increase in conjugated bilirubin. With reference to the recent literature in China and foreign countries, this article reviews the pathogenesis, genetic characteristics, diagnosis, treatment, and differential diagnosis of six types of hereditary congenital unconjugated jaundice.
- Jaundice /
- Gilbert Disease /
- Crigler-Najjar Syndrome /
- Jaundice, Chronic Idiopathic

HTML全文

表 1 先天性非溶血性黄疸的常见鉴别诊断

疾病名称	病因机制	遗传方式	主要临床表现	治疗
GS、CNS Ⅱ型	UGT1A1突变，肝细胞对胆红素醛酸化障碍	常染色体隐/显性	轻、中度的间歇、波动性黄疸	对症治疗(苯巴比妥等)
CNS Ⅰ型	UGT1A1突变，肝细胞对胆红素醛酸化障碍	常染色体隐/显性	重度黄疸、胆红素脑病	血浆置换、肝移植、光疗
Lucey-Driscoll综合征	机制不清(孕激素对新生儿UGT1A1抑制作用)	常染色体隐性	出生后重度黄疸、胆红素脑病	血浆置换、肝移植、光疗
母乳性黄疸	UGT1A1突变、母乳、肠道菌群等多重因素作用		轻、中度黄疸	继续母乳喂养或改配方奶粉
DJS	ABCC2基因突变，肝细胞对胆红素排泄障碍	常染色体隐性	轻、中度的间歇、波动性黄疸，可伴胆汁淤积	熊去氧胆酸等对症治疗
RS	SLCO1B1、SLCO1B3基因突变，肝细胞对胆红素摄取障碍	常染色体隐性	轻、中度的间歇、波动性黄疸等	对症治疗
Alagille综合征	JAG1或NOTCH2基因突变，NOTCH信号通路缺陷	常染色体显性	新生儿胆汁淤积、心血管异常、角膜后胚胎环、骨骼异常和特殊面容等	多学科联合治疗、胆汁分流术、肝移植^[37]
进行性家族性肝内胆汁淤积症(PFIC)/良性复发性肝内胆汁淤积症(BRIC)	PFIC1或BRIC1：ATP8B1基因突变 PFIC2或BRIC2：ABCB11基因突变 PFIC3：ABCB4突变 PFIC4：TJP2突变 PFIC5：NR1H4突变 PFIC6：MYO5B突变	常染色体隐性	持续性黄疸、瘙痒、白陶土样便、生长发育障碍、脂溶性维生素缺乏等	药物治疗(熊去氧胆酸、利福平、4-苯基丁酸酯、补充脂溶性维生素等)手术引流、肝移植^[38]
Citrin缺陷病(新生儿肝内胆汁淤积症)	SLC25A13基因突变，肝细胞利用葡萄糖、脂肪酸障碍	常染色体隐性	新生儿胆汁淤积、脂肪肝、低蛋白血症、凝血障碍、肝大、肝功能异常等	补充中链甘油三酯等对症治疗^[39]
先天性胆汁酸合成缺陷疾病	HSD3B7、AKR1D1、CYP7B1等基因突变，胆汁酸合成障碍	常染色体隐性	新生儿胆汁淤积、凝血功能障碍或脂溶性维生素吸收不良等	早期补充初级胆汁酸、肝移植^[40]

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