进行性家族性肝内胆汁淤积症4型的临床型及基因型分析  

Phenotype and genotype analysis of progressive familial intrahepatic cholestasis type 4

作　　者：杨亭亭[1] 马淑贞 吕玲[2] 陈源[1] 张亚男[1] 白欣立[1] Yang Tingting;Ma Shuzhen;Lyu Ling;Chen Yuan;Zhang Ya′nan;Bai Xinli(Department of Pediatrics,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China;Department of Endocrinology,Tianjin Children′s Hospital,Tianjin 300134,China)

机构地区：[1]河北医科大学第二医院儿科,石家庄050000 [2]天津市儿童医院内分泌科,天津300134

出　　处：《中华实用儿科临床杂志》2023年第6期457-460,共4页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的提高对进行性家族性肝内胆汁淤积症4型(PFIC4)的认识。方法回顾性分析2020年2月河北医科大学第二医院收治的1例10岁PFIC4患儿的临床特点,并对其TJP2基因突变进行分析。结果先证者,男,10岁,缓慢起病,以肝内胆汁淤积[γ-谷氨酰转肽酶(GGT)正常]、肝脾大、肝纤维化为主要临床表现。实验室检查:总胆红素升高,以结合胆红素升高为主;丙氨酸转氨酶、天冬氨酸转氨酶、总胆汁酸升高;GGT持续正常。初始口服熊去氧胆酸治疗,肝脏生化指标明显好转,后有波动。腺苷脱氢酶,凝血常规及肝纤维化四项持续异常;肝脏剪切波速度平均值达正常值上限1.9倍。TJP2基因发现复合杂合突变c.334G>A(p.A112T)/c.580_639delGACCGGAGCCGTGGCCGGAGCCTGGAGCGGGGCCTGGACCAAGACCATGCGCGCACCCGA(p.194_213del-DRSRGRSLERGLDQDHARTR),其中缺失突变为首次报道,父母各携带1个突变单链。结论对于肝内胆汁淤积伴正常范围的GGT患者应除外PFIC。TJP2基因检测在PFIC4的临床诊断中具有重要价值。TJP2突变可能是儿童早期发生肝硬化及原发性肝癌的危险因素,因此应密切随访监测PFIC4患儿情况。Objective To improve the understanding of progressive familial intrahepatic cholestasis type 4(PFIC4).Methods Clinical characteristics in a 10-year-old boy with PFIC4 at the Second Hospital of Hebei Medical University in February 2020 were retrospectively analyzed,and the TJP2 gene mutations were analyzed.Results The proband was a 10-year-old boy with a slow onset of intrahepatic cholestasis[normalγ-glutamyl transpeptidase(GGT)],hepatosplenomegaly and hepatic fibrosis.Laboratory tests showed elevated levels of total bilirubin,especially the direct bilirubin increased.Alanine aminotransferase,aspartate transaminase acid and total bile acid were elevated,while GGT remained in a normal range.Oral medication of ursodeoxycholic acid initially improved liver biochemical parameters,but later fluctuated.Adenosine dehydrogenase,coagulation indicators and hepatic fibrosis indexes were persistently abnormal.The average shear wave velocity of liver was 1.9 times of the upper limit of normal value.Compound heterozygous mutations c.334G>A(p.A112T)/c.580_639delGACCGGAGCCGTGGCCGGAGCCTGGAGCGGGG-CCTGGACCAAGACCATGCGCGCACCCGA(p.194_213delDRSRGRSLERGLDQDHARTR)were found in the TJP2 gene.The deletion mutation of the TJP2 gene was reported for the first time throughout the world.Both of his parents carried a heterozygous mutation.Conclusions PFIC should be considered in intrahepatic cholestasis patients with a normal range of GGT.The detection of TJP2 gene mutation is of great value in the clinical diagnosis of PFIC4.The presence of TJP2 gene mutation may be a risk factor for patient developing cirrhosis of liver and primary liver cancer in early childhood.It is necessary for children with PFIC4 to be closely followed up.

关 键 词：进行性家族性肝内胆汁淤积症4型 TJP2基因 紧密连接蛋白2 

分 类 号：R725.7[医药卫生—儿科]