mHS缺乏症1例并文献复习  

One case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency and literature review

作　　者：冉情 秦弦 罗佳美 周平 陈红兵 Ran Qing;Qin Xian;Luo Jiamei;Zhou Ping;Chen Hongbing(Department of Child Healthcare,Chongqing University Three Gorges Hospital,Chongqing 404100,China;Department of Gastroenterology,Chongqing University Three Gorges Hospital,Chongqing 404100,China)

机构地区：[1]重庆大学附属三峡医院儿童保健科,重庆404100 [2]重庆大学附属三峡医院儿童消化血液肾脏病区,重庆404100

出　　处：《中国基层医药》2022年第11期1670-1675,共6页Chinese Journal of Primary Medicine and Pharmacy

摘　　要：目的总结HMGCS2基因突变导致3-羟基-3-甲基戊二酰辅酶A合成酶2缺乏症(mHS缺乏症)患儿的临床表型及遗传学特点。方法2020年4月10日重庆大学附属三峡医院收治mHS缺乏症患儿1例,患儿因咳嗽、气促及深昏迷入院,入院后完善血尿气相色谱分析,对患儿行全外显子组高通量测序,并对突变基因的家系分布进行验证,诊断为mHS缺乏症。以“3-羟基-3-甲基戊二酰辅酶A合成酶2缺乏症”“HMGCS2”“mHS缺乏症”为检索词,分别在万方数据知识服务平台、中国期刊全文数据库、PubMed以及HGMD数据库检索截至2020年6月的相关文献,共检索到43例mHS缺乏症。总结HMGCS2基因突变患儿的临床表型和基因型。结果截至2020年6月,加上该例患儿,共有44例mHS缺乏症患儿,其中男性15例,女性11例,未知性别18例;年龄范围:0~24个月龄29例,>24个月龄4例,未发病6例,未知发病年龄5例;大多数患儿以发热、咳嗽、急性胃肠炎、昏迷等为首发症状,其中低血糖27例、代谢性酸中毒21例、肝肿大15例、FFA/D-3-HB升高16例、尿液4-羟基-6-甲基-2-吡喃酮(4HMP)(+)10例。该例患儿有肝大、丙氨酸氨基转移酶升高、代谢性酸中毒;尿气相色谱检测到多种代谢产物升高,血串联质谱检测C40升高,多种长链肉碱升高。全外显子组高通量测序显示HMGCS2基因有2个杂合突变,(NM_0055)c.559+1G>A;c.758 T>C杂合突变。使用Sanger测序进行验证及父母来源分析,发现突变分别来源于父母亲。该例患儿2个基因突变均属新发突变,在国内外均未见报道。根据ACMG序列变异解读标准与指南判定该变异为致病变异。结论当患儿有低酮症性低血糖和(或)代谢性酸中毒,FFA/D-3-HB和乙酰肉碱水平升高时,应考虑mHS缺乏症。HMGCS2基因检查可协助诊断。Objective To summarize the clinical phenotype and genetic characteristics of one child patient with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency(mHS)caused by HMGCS2 gene mutation.Methods One child patient with mHS who received treatment in Chongqing University Three Gorges Hospital on April 10,2020 was included in this patient.The child was hospitalized due to cough,shortness of breath and deep coma.After admission,gas chromatography-mass spectrometry of the blood and urine samples and high-throughput whole genome sequencing were performed.The pedigree of the child with gene mutation was analyzed.The child was diagnosed with mHS.Related publications published by June,2020 were searched in Wanfang database,Chinese Journal Full Text Database,PubMed and HGMD databases using search terms"mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency","HMGCS2""mHS deficiency".Forty-three papers addressing mHS deficiency were retrieved.The clinical phenotype and genotypes of the child with HMGCS2 mutation were summarized.Results As of June 2020,there were 44 children with mHS deficiency,including the child reported in this study.These children consisted of 15 males,11 females and 18 unknown genders.Among these children,29 were aged 0-24 months,4 were aged>24 months,6 had no symptoms,and 5 were of unknown age of disease onset.The first symptoms of most children were fever,cough,acute gastroenteritis,and coma.Twenty-seven children had hypoglycemia,21 children had metabolic acidosis,15 children developed hepatomegaly,16 children had increased FFA/D-3-HB,and 10 children were tested 4-hydroxy-6-methyl-2-pyrone positive.The child included in this study had hepatomegaly,elevated alanine aminotransferase and metabolic acidosis.Gas chromatography-mass spectrometry results showed that a variety of metabolites were increased.Tandem mass spectrometry results showed that C40 level was elevated,and long-chain carnitine contents were increased.High-throughput whole genome sequencing results revealed that there

关 键 词：3-羟基-3-甲基戊二酰辅酶A合成酶2缺乏症 HMGCS2基因 基因突变 低酮症性低血糖 代谢性酸中毒 FFA/D-3-HB 乙酰肉碱 

分 类 号：R725.9[医药卫生—儿科]