摘要目的 探讨遗传代谢筛查对婴儿胆汁淤积性肝病诊治的意义,并分析其中基因检测异常患儿的临床生化改变特征.方法 收集2016年1月至2017年1月就诊于中国医科大学附属盛京医院小儿消化内科的69例胆汁淤积性肝病患儿的临床资料,回顾性分析患儿的临床表现、体检特征、生化检验及遗传代谢筛查和基因检测结果.结果 69例患儿中,67例完善了血串联质谱分析和尿气相色谱‐质谱检测,遗传代谢筛查异常组患儿与正常组患儿相比碱性磷酸酶、总胆红素、直接胆红素、总胆汁酸水平升高,差异有统计学意义(P<0. 05).血串联质谱分析中最常见的异常是游离肉碱升高及精氨酸、瓜氨酸、甲硫氨酸升高,尿气相色谱‐质谱检测最常见的是3‐羟基丙酸、4‐羟基苯乳酸、4‐羟基苯乙酸等多种有机酸的升高. 6例基因检测结果为阳性的患儿中,4例Citrin缺陷引起的新生儿肝内胆汁淤积症患儿血尿串联质谱分析提示高氨基酸血症(瓜氨酸、酪氨酸)和尿有机酸升高;共有5种SLC25A13基因突变:IVS6+5G>A、851del4、IVS11+1G>A、851 854del以及852 855del. 1例进行性家族性肝内胆汁淤积症2型患儿表现为黄疸持续未退、重度瘙痒,化验血γ‐谷氨酰转肽酶正常,ABCB11基因的突变类型是c. 667C>T. 1例转醛醇酶缺乏症患儿TALDO1基因突变类型是c. 716G>A和c. 854dupA杂合突变.结论 血串联质谱分析和尿气相色谱‐质谱检测对遗传性胆汁淤积性肝病的早期筛查具有重要意义,基因检测可以为少见遗传代谢性疾病提供精确诊断.

abstractsObjective To assess the significance of screening for inherited metabolic diseases in the treatment and diagnosis of infantile cholestatic hepatopathy,and to analyze the biochemical changed character‐istics of patients who were diagnosed with gene mutations. Methods From January 2016 to January 2017,69 children who were diagnosed as intrahepatic cholestasis in the Pediatric Gastroenterology Department of Shengjing Hospital Affiliated to China Medical University were enrolled. The medical history,physical exami‐nation,biochemical test and genetic metabolism screening results were recorded. Results Sixty‐seven cases of 69 children made tandem mass spectrometry(MS/MS),gas chromatography‐mass spectrometry(GC/MS) or genetic testing. Compared with the normal hereditary metabolic disease screening group, the abnormal group had higher levels of alkaline phosphatase,total bilirubin,direct bilirubin,and total bile acid,the differ‐ence was statistically significant (P<0. 05). The most common abnormal in MS/MS were elevation of free carnitines and arginine,citrulline,methionine,and the most common abnormal in GC/MS were elevation of 3‐hydroxyl propionic acid,4‐hydroxyl phenyllactic acid,4‐hydroxyl phenylacetic acid. In 6 children with posi‐tive genetic test results,the MS/MS and GC/MS of 4 neonatal intrahepatic cholestasis caused by citrin defi‐ciency showed aminoacidemia(citrullinemia,tyrosinemia) and elevations of urine organic acids. Five muta‐tions of SLC25A13 gene were found in the neonatal intrahepatic cholestasis caused by citrin deficiency pa‐tients,including IVS6+5G >A,851del4,IVS11 +1G >A,851 854de and 852 855del. The main clinical manifestations of progressive familial intrahepatic cholestasis type 2 ( PFIC2) were cholestatic jaundice and pruritus,γ‐glutamyl transpeptidase was normal,and with the c. 667C>T defection in the ABCB11 gene. The TALDO1 gene mutation type of one transaldolase deficiency was c. 716G>A and c. 854dupA heterozygous mutation. Conclusion MS/MS and GC/MS play a vital role in the early identification of cholestasis caused by genetic and metabolic disorders. Genetic testing can provide accurate diagnosis for rare genetic metabolic diseases.