LIPT1复合杂合变异致新生儿硫辛酰基转移酶-1缺乏症1例并文献复习  

Compound heterozygous variants in LIPT1 causing lipoyltransferase 1 deficiency in a newborn:a case report and literature review

作　　者：朱莹莹 翁博雯 许无恨 高莉 胡豪 龚小慧[1] 孙婧婧[1,4] Zhu Yingying;Weng Bowen;Xu Wuhen;Gao Li;Hu Hao;Gong Xiaohui;Sun Jingjing(Department of Neonatology,Shanghai Children's Hospital(Shanghai Children's Hospital,School of Medicine,Shanghai Jiao Tong University),Shanghai 200062,China;Department of Clinical Laboratory,Shanghai Children's Hospital(Shanghai Children's Hospital,School of Medicine,Shanghai Jiao Tong University),Shanghai 200062,China;Department of Pathology,Shanghai Changhai Hospital(the First Affiliated Hospital of Naval Medical University),Shanghai 200433,China;Key Laboratory of Medical Embryology and Molecular Biology,National Health Commission(Shanghai Key Laboratory of Embryology and Reproductive Engineering),Shanghai 200040,China)

机构地区：[1]上海市儿童医院(上海交通大学医学院附属儿童医院)新生儿科,上海200062 [2]上海市儿童医院(上海交通大学医学院附属儿童医院)检验科,上海200062 [3]上海长海医院(海军军医大学第一附属医院)病理科,上海200433 [4]国家卫健委医学胚胎分子生物学重点实验室(上海市胚胎与生殖工程重点实验室),上海200040

出　　处：《中华围产医学杂志》2024年第5期411-416,共6页Chinese Journal of Perinatal Medicine

摘　　要：目的探讨硫辛酰基转移酶-1缺乏症(lipoyltransferase 1 deficiency,LIPT1D)的临床表型和基因型特点。方法回顾性分析2023年5月7日上海市儿童医院新生儿科收治的1例LIPT1D患儿的临床资料。以“硫辛酰基转移酶-1缺乏症”“LIPT1”“硫辛酸”为关键词在中国知网、万方数据库、维普数据库和中华医学期刊全文数据库,以“Lipoyltransferase 1 deficiency”“LIPT1”“Lipoic acid”为关键词在PubMed、Embase、Web of Science数据库检索建库至2023年9月15日发表的相关文献。总结LIPT1D的临床表现、生化表型和基因型特点。采用描述性统计分析。结果(1)本例患儿:生后1.5 h出现青紫、反应差,表现为难以纠正的代谢性酸中毒(血气pH值6.9,碱剩余-27 mmol/L,碳酸氢根5.7 mmol/L)和高乳酸血症(最高24 mmol/L),病情进展快,生后9 h死亡。生后6 h取血送检家系全外显子组测序,检出患儿LIPT1基因(NM_001204830.1)存在复合杂合变异,分别为来自母亲的c.986C>A(p.Ser329*)和来自父亲的c.405_406del(p.Arg135Serfs*18),均为疑似致病变异。(2)文献复习:共检索到LIPT1基因变异所致LIPT1D病例7例,加之本例,共8例。LIPT1D患儿主要表现为严重高乳酸血症、代谢性酸中毒、神经发育迟缓以及癫痫,其中4例在新生儿期发病并死亡。结论LIPT1D患儿主要临床表现为严重高乳酸血症、代谢性酸中毒和神经系统受累,可导致新生儿早期死亡,全外显子组测序对疾病诊断具有重要意义。Objective To investigate the clinical phenotype and genotype characteristics of lipoyltransferase 1 deficiency(LIPT1D).Methods A retrospective analysis of the clinical data was conducted for one case of LIPT1D,admitted to the Department of Neonatology at Shanghai Children's Hospital on May 7,2023.Key terms"lipoyltransferase 1 deficiency","LIPT1",and"lipoic acid"were used to search national databases including CNKI,Wanfang Data,VIP,and Yigle;and international databases PubMed,Embase,and Web of Science until September 15,2023,to summarize the clinical presentations,biochemical phenotypes,and genotypic characteristics of LIPT1D.Descriptive statistical analysis was employed.Results(1)The case concerned:At 1.5 h after birth,the infant exhibited cyanosis and poor responsiveness,presenting with uncorrectable metabolic acidosis(blood pH value 6.9,base excess-27 mmol/L,bicarbonate 5.7 mmol/L),and hyperlactatemia(the highest was 24 mmol/L).The condition progressed rapidly,and the infant died 9 h after birth.Whole exome sequencing performed 6 h postnatally identified compound heterozygous variants in the LIPT1 gene(NM_001204830.1)in the infant.Variants c.986C>A(p.Ser329*)from the mother and c.405_406del(p.Arg135Serfs*18)from the father were detected,both suspected to be pathogenic.(2)Literature review:A review of the literature identified seven cases of LIPT1D caused by LIPT1 gene mutations,totaling eight cases including the current one.The main presentations of LIPT1D in these infants were hyperlactatemia,metabolic acidosis,neurodevelopmental delay,and epilepsy,with four cases presenting in the neonatal period and resulting in death.Conclusions The primary clinical manifestations of LIPT1D are severe hyperlactatemia,metabolic acidosis,and neurological involvement,potentially leading to early neonatal death.Whole-exome sequencing is instrumental in diagnosing this condition.

关 键 词：硫辛酰基转移酶-1缺乏症 LIPT1基因 硫辛酸 乳酸酸中毒 

分 类 号：R722.1[医药卫生—儿科]