MRPS34基因变异致联合氧化磷酸化缺陷症32型1例并文献复习  

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review

作　　者：沈梦晓 姬辛娜[1] 吴凡 高彦彦 冯硕[1] 谢丽娜[1] 郑萍[1] 毛莹莹[1] 陈倩[1] Shen Mengxiao;Ji Xinna;Wu Fan;Gao Yanyan;Feng Shuo;Xie Lina;Zheng Ping;Mao Yingying;Chen Qian(Department of Neurology,Children′s Hospital,Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院神经内科,北京100020

出　　处：《中华儿科杂志》2023年第7期642-647,共6页Chinese Journal of Pediatrics

基　　金：国家重点研发计划(2022YFC2703903);吴阶平医学基金会临床科研专项(320.6750.2021-04-33)。

摘　　要：目的总结MRPS34基因变异致联合氧化磷酸化缺陷症32型(COXPD32)的临床表型及基因型特点。方法回顾性分析2021年3月首都儿科研究所附属儿童医院收治的1例MRPS34基因变异致COXPD32患儿的临床资料及遗传学检测结果,并以"联合氧化磷酸化缺陷症32型""MRPS34基因"或"combined oxidative phosphorylation deficiency 32""MRPS34 gene"为关键词分别检索中国知网、万方和中国生物医学文献数据库或ClinVar、人类基因组突变数据库(HGMD)和PubMed数据库建库至2023年2月的文献。总结COXPD32的临床表型及基因型特点。结果患儿,男,1岁9月龄,因"发育迟滞"入院。患儿语言及运动发育落后,眼神接触差,身高、体重及头围均低于同年龄同性别儿童P3。双眼内斜视,鼻梁低平,胸骨左缘闻及Ⅲ/6级收缩期杂音,四肢肌张力减低,持物不稳,存在意向性及静止性震颤。血气分析示重度代谢性酸中毒并乳酸酸中毒;头颅磁共振成像示双侧丘脑、中脑、脑桥及延髓多发对称性异常信号;心脏多普勒超声示房间隔缺损;基因检测示MRPS34基因c.580C>T(p.Gln194Ter)和c.94C>T(p.Gln32Ter)复合杂合变异,分别遗传自其父母,c.580C>T(p.Gln194Ter)为首次报道,诊断为COXPD32。予保证能量、纠正酸中毒、左卡尼汀口服液改善能量代谢及维生素B1、维生素B2、维生素B6、维生素C、辅酶Q10"鸡尾酒"疗法等治疗后患儿病情好转。文献检索到中文文献0篇,英文文献2篇,结合本例共8例患者。7例患者婴儿期内起病,1例不详。8例患者均存在生长发育迟滞或倒退,7例有喂养困难或吞咽困难,其余症状为肌张力障碍、眼部症状、小头畸形、便秘及特殊面容(皮肤粗糙、前额小、发际线低至前额、眉毛粗重、上腭高窄呈"V"形、牙龈厚、鼻小柱短及连眉)等;2例死于呼吸循环衰竭,6例报道时仍存活,年龄范围为2~34岁。8例患者均有血和(或)脑脊液乳酸升高。7例头颅磁共振成�Objective To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32(COXPD32)caused by MRPS34 gene variation.MethodsThe clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology,Children′s Hospital,Capital Institute of Pediatrics in March 2021 were extracted and analyzed.A literature search was implemented using Wanfang,China biology medicine disc,China national knowledge infrastructure,ClinVar,human gene mutation database(HGMD)and Pubmed databases with the key words"MRPS34""MRPS34 gene"and"combined oxidative phosphorylation deficiency 32"(up to February 2023).Clinical and genetic features of COXPD32 were summarized.ResultsA boy aged 1 year and 9 months was admitted due to developmental delay.He showed mental and motor retardation,and was below the 3rd percentile for height,weight,and head circumference of children of the same age and gender.He had poor eye contact,esotropia,flat nasal bridge,limbs hypotonia,holding instability and tremors.In addition,GradeⅢ/6 systolic murmur were heard at left sternal border.Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis.Brain magnetic resonance imaging(MRI)showed multiple symmetrical abnormal signals in the bilateral thalamus,midbrain,pons and medulla oblongata.Echocardiography showed atrial septal defect.Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene,c.580C>T(p.Gln194Ter)and c.94C>T(p.Gln32Ter),with c.580C>T being the first report and a diagnosis of COXPD32.His parents carried a heterozygous variant,respectively.The child improved after treatment with energy support,acidosis correction,and"cocktail"therapy(vitaminB1,vitaminB2,vitaminB6,vitaminC and coenzyme Q10).A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study.Among the 8 patients,7 cases had onset during infancy and 1 was unknown,all had developmental delay or regression,7 cases had feeding difficulty or

关 键 词：线粒体疾病 基因 MRPS34 联合氧化磷酸化缺陷症 

分 类 号：R725.9[医药卫生—儿科]