新生儿期发病的特发性胆汁淤积症基因诊断分析  

The genetic diagnosis of idiopathic cholestasis of neonatal onset

作　　者：胡晓越 任春艳[1] 米荣[1] 康利民[1] 王建华[2] 吕岩玉[1] 李莉[1] Hu Xiaoyue;Ren Chunyan;Mi Rong;Kang Limin;Wang Jianhua;Lyu Yanyu;Li Li(Neonatal Department,Children's Hospital Affiliated to the Capital Institute of Pediatrics,Beijing 100020,China;Beijing Municipal Key Laboratory of Child Development and Nutriomics,Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院新生儿内科,北京100020 [2]首都儿科研究所儿童发育营养组学北京市重点实验室,100020

出　　处：《中华新生儿科杂志（中英文）》2021年第2期22-26,共5页Chinese Journal of Neonatology

摘　　要：目的探讨新生儿期发病的特发性胆汁淤积症患儿的基因型特点。方法选择2015年11月至2018年11月首都儿科研究所附属儿童医院新生儿内科收治的特发性胆汁淤积症并完成全外显子测序检查的患儿进行回顾性分析,根据患儿基因检测结果分为病因明确组和病因未明组,分析两组患儿基因检测结果,并比较两组患儿1岁时胆红素水平。结果共纳入特发性胆汁淤积症患儿62例,均为汉族,男43例(69.4%);均在新生儿期发病,起病日龄<7 d 39例,7~14 d 9例,>14 d 14例。病因明确组16例,其中希特林蛋白缺乏症4例,Alagille综合征2例,进行性家族性胆汁淤积症1型和2型、半乳糖血症、瓜氨酸血症Ⅰ型、巨大舌-脐膨出综合征、关节挛缩-肾功能不全和胆汁淤积综合征、Menkes病、先天性胆汁酸合成障碍、D-双功能蛋白缺乏症、Dubin-Johnson综合征各1例;病因未明组46例。随访至1岁时,病因明确组胆红素异常比例高于病因未明组,差异有统计学意义(P=0.001)。结论全外显子测序可明确部分特发性胆汁淤积症患儿的病因,诊断结果有助于判断预后。胆汁淤积症患儿的遗传学病因较分散,希特林蛋白缺乏症、Alagille综合征及进行性家族性胆汁淤积症占比较高。Objective To study the genetic characteristics of idiopathic cholestasis during the neonatal period.Method From November 2015 to November 2018,neonatal infants with idiopathic cholestasis admitted to the neonatal department of our hospital and completed the whole exon sequencing(WES)were retrospectively analyzed.According to the WES results,the infants were assigned into two groups,the etiology-determined group and the etiology-undetermined group.The bilirubin levels of the two groups at one-year-old were compared.Result A total of 62 Han infants were enrolled,including 43 males and 19 females.The age of onset was<7 d in 39 cases,7~14 d in 9 cases and>14 d in 14 cases.16 infants were in the etiology-determined group,including 4 cases of neonatal intrahepatic cholestasis of citrin deficiency(NICCD),2 cases of Alagille syndrome,1 case of progressive familial cholestasis type 1 and 2,galactosemia,citrullinemia typeⅠ,Beckwith-Wiedemann syndrome,arthrogryposis-renal-dysfunction-cholestasis syndrome,Menkes disease,congenital bile acid synthesis disorder,D-difunctional protein deficiency and Dubin-Johnson syndrome.46 infants were in the etiology-undetermined group.At 1 year of follow-up,the proportion of infants with abnormal bilirubin in the etiology-determined group was higher than the etiology-undetermined group(P=0.001).Conclusion WES technology can identify the etiology and predict the prognosis in some of the infants with idiopathic neonatal hepatitis.While neonatal cholestasis may have many genetic causes,NICCD,Alagille syndrome and progressive familial cholestasis are relatively common.

关 键 词：胆汁淤积 病因 婴儿 新生 基因 全外显子测序 

分 类 号：R722.1[医药卫生—儿科] R440[医药卫生—临床医学]