一例NTCP缺陷合并Alagille综合征病例报道并文献复习

摘要/Abstract

摘要： 目的探讨牛磺酸共转运多肽(NTCP)缺陷合并Alagille综合征(ALGS)儿童的临床及基因变异特征。方法回顾分析1例NTCP缺陷合并ALGS患儿的临床资料及基因学检测结果,并复习相关文献。结果患儿,男童,4月龄,生后1周出现皮肤巩膜黄染,有特殊面容,前额突出,眼深陷和尖下巴。生化检查提示血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、胆汁酸(TBA)、胆红素(TBil)明显升高,但γ-谷氨酰转肽酶(GGT)不高。基因组测序提示患儿JAG1基因点发生杂合突变,c.1148_1149del,致氨基酸p.C383fs(383位半胱氨基及下游氨基酸)被改变,同时于SLC10A1发生纯合突变 c800C>T,致氨基酸p.s267F(267位丝氨酸被苯丙氨酸替换)改变,确诊为NTCP缺陷合并ALGS。结论 NTCP缺陷合并ALGS可表现为低GGT的胆汁淤积性肝炎,基因检测有助于明确诊断。

关键词: Alagille综合征, 胆汁淤积, 基因突变, 牛磺酸共转运多肽缺陷

Abstract: Objective To investigate the clinical features and genetic variation characteristics in children with a sodium taurocholate co-transporting polypeptide (NTCP) deficiency combined with Alagille syndrome (ALGS). Methods The clinical data and genetic test results of a child with NTCP deficiency combined with ALGS were retrospectively analyzed, along with a review of relevant literature. Results The patient, a 4-month-old boy, presented with jaundice of the skin and sclera one week after birth. He displayed characteristic facial features, including a prominent forehead, deep-set eyes, and a pointed chin. Laboratory findings revealed significant elevations in serum ALT, AST, TBA, and TBil, with no marked increase in γ-GT. Genomic sequencing identified a heterozygous mutation at the JAG1 gene locus( c.1148_1149del), resulting in a frameshift mutation altering the amino acid at p.C383fs (cysteine in the 383rd position and downstream amino acid), and a homozygous mutation at the SLC10A1 locus( c800C>T), changing the amino acid at p.s267F (serine in the 267th position was replaced by phenylalanine). Based on these findings, the patient was diagnosed with NTCP deficiency combined with ALGS. Conclusion NTCP deficiency combined with ALGS may manifest as low-γ-GT cholestatic hepatitis, and genetic testing is valuable for diagnostic confirmation.

Key words: Alagille syndrome, Cholestasis, Gene variant, Sodium taurocholate cotransporting polypeptid deficiency

佘兰辉, 李旭芳, 房春晓, 刘世英, 徐翼. 一例NTCP缺陷合并Alagille综合征病例报道并文献复习[J]. 肝脏, 2024, 29(11): 1422-1426.

SHE Lan-hui, LI Xu-fang, FANG Chun-xiao, LIU Shi-ying, XU Yi. NTCP deficiency combined with Alagille Syndrome: a case report and literature review[J]. Chinese Hepatolgy, 2024, 29(11): 1422-1426.

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