Lee Su Jeong, Kim Jung Eun, Choe Byung-Ho, Seo An Na, Bae Han-Ik, Hwang Su-Kyeong
Department of Pediatrics, Kyungpook National University School of Medicine, Daegu, Korea.
Department of Pathology, Kyungpook National University School of Medicine, Daegu, Korea.
Pediatr Gastroenterol Hepatol Nutr. 2017 Jun;20(2):114-123. doi: 10.5223/pghn.2017.20.2.114. Epub 2017 Jun 28.
The goal of this study was the early diagnosis of spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis.
Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or spectrum liver disorders. Two families with proven spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling. Whole exome sequencing and Sanger sequencing were performed on the patients and the family members.
Idiopathic or viral hepatitis was diagnosed in 34%, metabolic disease in 20%, total parenteral nutrition induced cholestasis in 16%, extrahepatic biliary atresia in 14%, genetic disease in 10%, neonatal lupus in 2%, congenital syphilis in 2%, and choledochal cyst in 2% of the patients. The patient with progressive familial intrahepatic cholestasis had novel heterozygous mutations of c.11C>G (p.Ser4) and c.1543A>G (p.Asn515Asp). The patient with benign recurrent intrahepatic cholestasis had homozygous mutations of c.1331T>C (p.Val444Ala) and heterozygous, c.3084A>G (p.Ala1028Ala). Genetic confirmation of spectrum liver disorder led to early liver transplantation in the progressive familial intrahepatic cholestasis patient. In addition, the atypically severe benign recurrent intrahepatic cholestasis patient was able to avoid unnecessary liver transplantation after genetic analysis.
spectrum liver disorders can be clinically indistinguishable as they share similar characteristics related to acute episodes. A comprehensive genetic analysis will facilitate optimal diagnosis and treatment.
本研究的目标是对一系列肝脏疾病进行早期诊断，尤其是那些以良性复发性肝内胆汁淤积症和进行性家族性肝内胆汁淤积症为重点的疾病。
对50例出现新生儿胆汁淤积症的患者进行评估，以确定潜在病因。对疑似患有综合征性疾病或一系列肝脏疾病的患者进行基因分析。对两个已证实患有一系列肝脏疾病的家庭进行基因分析以确诊，并为其提供遗传咨询。对患者及其家庭成员进行全外显子组测序和桑格测序。
34%的患者被诊断为特发性或病毒性肝炎，20%为代谢性疾病，16%为全胃肠外营养所致胆汁淤积症，14%为肝外胆管闭锁，10%为遗传性疾病，2%为新生儿狼疮，2%为先天性梅毒，2%为胆总管囊肿。患有进行性家族性肝内胆汁淤积症的患者有新的杂合突变c.11C>G（p.Ser4）和c.1543A>G（p.Asn515Asp）。患有良性复发性肝内胆汁淤积症的患者有纯合突变c.1331T>C（p.Val444Ala）和杂合突变c.3084A>G（p.Ala1028Ala）。一系列肝脏疾病的基因确诊使得进行性家族性肝内胆汁淤积症患者得以早期进行肝移植。此外，非典型严重良性复发性肝内胆汁淤积症患者在基因分析后能够避免不必要的肝移植。
一系列肝脏疾病在临床上可能难以区分，因为它们在急性发作方面具有相似特征。全面的基因分析将有助于优化诊断和治疗。
