核基因变异致新生儿原发性线粒体疾病4例临床和基因分析  

Neonatal-onset primary mitochondrial disease caused by nuclear gene mutations:a report of 4 cases

作　　者：崔清洋 尚云[1] 孙亚洲 桑桂梅 李雯[2] 贺晓日[2] 龚晓云 Cui Qingyang;Shang Yun;Sun Yazhou;Sang Guimei;Li Wen;He Xiaori;Gong Xiaoyun(Department of Pediatrics,the First Affiliated Hospital of Xinxiang Medical College,Weihui 453100,China;Division of Neonatology,Children's Medical Center,Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]新乡医学院第一附属医院儿科,卫辉453100 [2]中南大学湘雅二医院儿童医学中心新生儿专科,长沙410011

出　　处：《中华新生儿科杂志（中英文）》2024年第1期34-37,共4页Chinese Journal of Neonatology

基　　金：新乡医学院第一附属医院博士科研启动基金(xyyfy2019BS-005)。

摘　　要：目的探讨核基因变异致新生儿原发性线粒体疾病患儿的临床表现和基因变异特点。方法收集2020年5月至2022年3月新乡医学院第一附属医院新生儿科和中南大学湘雅二医院新生儿专科收治的核基因变异致新生儿原发性线粒体疾病患儿的临床资料、基因检测结果及随访信息进行回顾性分析。结果共纳入4例患儿,均有高乳酸血症和代谢性酸中毒;病例1母孕期胎儿头颅磁共振成像示胼胝体缺如,病例2生后心脏彩超提示肥厚性心肌病。全外显子检测示4例患儿分别携带EARS2核基因c.1294C>T变异及c.971G>T变异,COA6核基因c.411412insAAAG变异,ACAD9核基因c.1278+1G>A变异及c.895A>T变异,FOXRED1核基因c.1054C>T变异及c.3dup变异。线粒体二代测序及多重连接探针扩增未发现异常。病例1和病例3于新生儿期死亡,病例2于2岁2个月时死亡,病例4随访至1岁生长发育落后。结论核基因变异所致新生儿原发性线粒体疾病主要表型为高乳酸血症、顽固性代谢性酸中毒,预后较差,积极基因检测有助于早期诊断。Objective To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease(PMD)caused by nuclear gene mutations.Methods From May 2020 to March 2022,the clinical data,genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results A total of 4 patients were enrolled,all with hyperlactatemia and metabolic acidosis.In case 1,the fetal cranial MRI showed agenesis of corpus callosum.In case 2,echocardiography after birth indicated hypertrophic cardiomyopathy.Whole exome sequencing found the following mutations:EARS2 nuclear gene c.1294C>T and c.971G>T variants,COA6 nuclear gene c.411_412insAAAG variant,ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants,FOXRED1 nuclear gene c.1054C>T and c.3dup variants.Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities.Cases 1 and 3 died during the neonatal period.Case 2 died at 2-year-and-2-month of age.Case 4 was followed up to 1 year of age with developmental delay.Conclusions The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia,refractory metabolic acidosis and cardiomyopathy,which have a poor prognosis.Proactive genetic tests are helpful for early diagnosis.

关 键 词：原发性线粒体疾病 核基因 新生儿 高乳酸血症 心肌病 

分 类 号：R722.1[医药卫生—儿科]