联合型氧化磷酸化缺陷症17型一例报道并文献复习

Combined oxidative phosphorylation deficiency type 17:a case report and literature review

目的总结1例联合型氧化磷酸化缺陷症17型(COXPD-17)患儿的临床表现和ELAC2基因变异特点,结合文献复习,总结ELAC2基因型-表型关系,为该病的诊断、治疗和遗传咨询提供依据。方法回顾性分析2024年5月我院PICU确诊的1例COXPD 17缺陷症患儿的临床资料,并以“联合氧化磷酸化缺陷症17型、ELAC2基因”或“combined oxidative phosphorylation deficiency 17、ELAC2 gene”为检索词查阅国内外数据库,总结COXPD-17的临床特点及ELAC2基因变异特点。结果7月女患儿,平素有吃奶停顿、汗多。本次主要表现为呼吸急促、颜面发绀,尿少入院,查体:颜面青紫,心脏及肝脏增大。辅查:乳酸增高,肌钙蛋白及BNP异常增高,心脏彩超:左室增大,左室射血分数下降。经积极强心、利尿、扩血管,营养心肌,血液净化等治疗抢救无效死亡。将父母及患儿的外周血进行基因检查显示ELAC2基因复合杂合变异:c.1585G>A(p.Gly529Arg)及c.524A>C(p.Asp175Ala),经Sanger测序验证分析,两个位点分别来源于受检人父母,两个位点均未见报道。文献报道27例患者,加上本例28例患儿的表型有心力衰竭、心肌病、心包积液、乳酸增高、宫内发育不良、全面生长缓慢、肌张力低下、小头畸型、癫痫等。20例(71.4%)患儿死于心力衰竭。分析ELAC2基因突变位点与临床表型的相关性,发现突变在靠近tRNA 3′端时,发病早,多数死于心力衰竭。结论COXPD-17是一种常染色体隐性遗传的多系统受累疾病,ELAC2基因变异是其致病原因。总体预后差,目前无特效治疗,多死于心力衰竭,幸存者遗留神经系统后遗症。早期精准诊断,及时产前咨询是预防该病的主要手段。

Objective To summarize the clinical manifestations of Combined oxidative phosphorylation deficiency(COXPD-17)with ELAC2 gene variation in a child,and to summarize the genotypic and phenotypic characteristic of ELAC2 based on literature review,so as to provide basis for diagnosis,treatment and genetic counseling for COXPD-17 patients.Methods The clinical data of a child diagnosed with COXPD-17 in PICU of our hospital in May 2024 were retrospectively analyzed.And“combined oxidative phosphorylation deficiency 17,ELAC2 gene”or“Combined oxidative phosphorylation deficiency 17,ELAC2 gene”were used as search terms to consult domestic and international databases.The clinical characteristics of COXPD-17 and the variation of ELAC2 gene were summarized.Results The patient,a 7 month-old female,exhibited symptoms such as feeding pauses and excessive sweating.The main manifestations for hospitalization included shortness of breath,facial cyanosis andoliguria.Facial cyanosis,heart and liver enlargement were observed in physical examination.Increased lactic acid,significant elevated troponin and BNP were noticed in laboratory tests.Echocardiography showed left ventricular enlargement and decreased left ventricular ejection fraction.Although aggressive treatments including heart strengthening,diuresis,vasodilation,myocardial nourishing myocardium,and blood purification were performed,the resuscitation efforts were unsuccessful.Genetic analysis of the peripheral blood from the child and the parents showed complex heterozygous variation of ELAC2 gene:c.1585G>A(p.Gly529Arg)and c.524A>C(p.Asp175Ala).Sanger sequencing analysis confirmed that the two loci were inherited from the parents of the patients,and neither of locus has been previously reported.The phenotypes of 28 patients including our case were documented in the literature,primarily manifestations including heart failure,cardiomyopathy,pericardial effusion,elevated lactic acid,intrauterine dysplasia,overall growth retardation,hypotonia,microcephaly,and epilepsy.Among them 20patients(71.4%)died of heart failure.The correlation between ELAC2 gene mutation site and clinical phenotype was analyzed,revealing that mutations occurring near the 3′end of tRNA were associated with an earlier onset of the disease,with the majority of patients ultimately dying from heart failure.Conclusion COXPD-17 is an autosomal recessive disease involved in multi-system,and the mutation of ELAC2 gene was identified as a potential etiology.The overall prognosis for affected population is poor,as there is no specific available treatment at present,most of the deaths attributed to heart failure.Most survivors may experience neurological sequelae.Therefore,early accurate diagnosis and timely prenatal consultation play a vital role in preventing the disease.