钠牛磺胆酸共转运多肽缺陷病临床特征及SLC10A1基因突变分析

Clinical features of sodium taurocholate cotransporting polypeptide deficiency and an analysis of SLC10A1 gene mutation

目的总结钠牛磺胆酸共转运多肽(NTCP)缺陷病的临床和基因突变特征。方法选取2020年6月—2021年6月于广州市妇女儿童医疗中心经基因检测确诊的10例NTCP缺陷病患儿(年龄<18岁),分析一般资料(性别、年龄、身高、体质量、家族史和既往病史)、临床表现、病情转归、实验室检查(血常规、肝功能、嗜肝病毒、自身免疫性肝炎筛查)及基因突变检测结果。结果10例患儿生长发育均正常,其中男8例,女2例;确诊年龄3~37个月。首次就诊病因包括新生儿黄疸延长(5/10,50%)、转氨酶升高(2/10,20%)、体检(2/10,20%)和肺炎(1/10,10%)。所有患儿确诊时血清TBA水平均明显升高;ALT、AST水平升高2例;TBil水平升高1例,且以DBil水平升高为主(DBil/TBil>50%)。经第二代基因测序,10例患儿均为SLC10A1基因纯合突变:c.800C>T(p.Ser267Phe,chr14∶70245193)。结论尽管NTCP缺乏症往往无明显症状,但部分患儿早期可表现为婴儿胆汁淤积症,对于显著而持续的高胆汁酸血症,且血清总TBA水平与其他肝功能指标的变化趋势不一致时,应考虑NTCP缺陷病可能。

Objective To investigate the clinical and gene mutation features of sodium taurocholate cotransporting polypeptide(NTCP)deficiency.Methods A total of 10 children,aged<18 years,who were diagnosed with NTCP deficiency in Guangzhou Women and Children’s Medical Center from June 2020 to June 2021 were enrolled,and related data were analyzed,including general information(sex,age,body height,body weight,family history,and past history),clinical manifestation,disease outcome,laboratory examination(routine blood test,liver function,hepatotropic virus,and autoimmune hepatitis screening),and gene mutation.Results All 10 children had normal growth and development,among whom there were 8 boys and 2 girls,with an age of 3-37 months at the time of diagnosis.The etiology of children attending the hospital for the first time was prolonged jaundice(5/10,50%),elevation of aminotransferases(2/10,20%),abnormal physical examination results(2/10,20%),and pneumonia(1/10,10%).At the time of diagnosis,all children had a significant increase in serum total bile acid(TBA),2 children had increases in alanine aminotransferase and aspartate aminotransferase,and 1 child had an increase in total bilirubin(TBil),mainly direct bilirubin(DBil)(DBil/TBil ratio>50%).Second-generation gene sequencing showed that all 10 children had a homozygous mutation of the SLC10A1 gene,i.e.,c.800C>T(p.Ser267Phe,chr14∶70245193).Conclusion Although NTCP deficiency often has no symptoms,some of the children may manifest as infant cholestasis in the early stage.The possibility of NTCP deficiency should be considered when there is persistent hypercholanemia and the changing trend of serum TBA is not consistent with that of other liver function parameters.