NBAS基因变异致儿童急性肝功能衰竭4例的临床特征及遗传学研究  

Clinical features and genetic study of four cases of pediatric acute liver failure caused by NBAS gene variants

作　　者：余金丹[1] 赵泓[1] 方优红[1] 罗优优[1] 楼金玕[1] 陈洁[1] Yu Jindan;Zhao Hong;Fang Youhong;Luo Youyou;Lou Jingan;Chen Jie(Department of Gastroenterology,Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310057,China)

机构地区：[1]浙江大学医学院附属儿童医院消化科、国家儿童健康与疾病临床医学研究中心,杭州310057

出　　处：《中华肝脏病杂志》2025年第2期170-176,共7页Chinese Journal of Hepatology

基　　金：国家自然科学基金区域创新发展联合基金项目(U23A20167);浙江省医药卫生科技计划项目(2024KY1171)。

摘　　要：目的探讨神经母细胞瘤扩增序列(NBAS)基因变异致儿童急性肝功能衰竭4例患儿的临床特征,并分析其临床表型与基因型的相关性。方法回顾性分析2015年8月至2023年6月在浙江大学医学院附属儿童医院消化科收治的4例以儿童急性肝功能衰竭(PALF)为主要表现的NBAS基因变异患儿的临床资料及基因检测结果。以“NBAS”“neuroblastoma amplified sequence”“SOPH”“short stature with optic nerve atrophy and Pelger-Huët anomaly”“肝衰竭”“神经母细胞瘤扩增序列”为中英文关键词,检索2015年1月至2024年5月的中国知网数据库、万方数据知识服务平台和PubMed数据库收录的相关文献,总结国内患者的临床特征和基因变异位点。结果4例患儿的PALF首次发作年龄为8个月至3岁7个月。所有患儿在发热后1~2 d内出现PALF,症状包括呕吐、抽搐、精神萎靡或神志不清等,伴随转氨酶急剧上升,胆红素和血氨升高,高乳酸血症和肝脏肿大。经过退热、补液及其他对症支持治疗后,患儿的PALF逐渐好转,其中3例另表现出肝外症状。在长期随访过程中,通过积极的体温控制和对症处理,可减少患儿PALF的反复发作。基因检测共发现8种NBAS基因变异位点,经家系验证均为复合杂合变异,包括4种错义变异、1种无义变异和3种移码变异。文献回顾共纳入51例国内NBAS基因变异患者,发现98.0%(50/51)的患者存在肝脏受累,其中37例表现为PALF。共发现61种变异位点,其中c.3596G>A(45.1%,23/51)为热点变异。结论NBAS基因变异导致的PALF具有明显的临床和遗传学特征,且存在基因型与临床表型的相关性。NBAS:c.3596G>A在国内为热点变异,与肝衰竭表型有较强的关联性。Objective To analyze the clinical and genetic features of four children with pediatric acute liver failure(PALF)caused by neuroblastoma-amplified sequence(NBAS)gene variant,as well as the correlation between clinical phenotype and genotype.Methods The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology,Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure(PALF)were retrospectively analyzed.The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords"NBAS,""neuroblastoma amplified sequence,""SOPH,""short stature with optic nerve atrophy and Pelger Huët anomaly,""liver failure,"and"neuroblastoma amplified sequence"indexed in the CNKI database,Wanfang Data Knowledge Service Platform,and PubMed database.The clinical features and gene mutation characteristics of domestic patients were summarized.Results The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months.All patients developed PALF within 1-2 days after the onset of fever,with symptoms such as vomiting,convulsions,and mental depression or confusion,accompanied by a sharp increase in transaminases,elevated bilirubin and blood ammonia,hyperlactatemia,and hepatomegaly.The PALF gradually improved,and three pediatric patients showed extrahepatic manifestations following antipyretic,fluid replacement,and other symptomatic supportive treatment.Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF.Genetic testing identified eight kinds of NBAS gene variants sites.Family testing validated compound heterozygous variants,which included four missense variants,one nonsense variants,and three frameshift mutations.A literature study revealed that out of 51 Chinese patients with NBAS gene variants,98.0%(50/51)had liver involvement

关 键 词：肝功能衰竭 儿童 NBAS基因 婴儿肝功能衰竭综合征2型 遗传 诊断 

分 类 号：R72[医药卫生—儿科]