ACSF3基因突变所致联合性丙二酸甲基丙二酸尿症一例

Combined malonic methylmalonic aciduria caused by ACSF3 gene mutation:a case report

目的 探讨联合性丙二酸甲基丙二酸尿症(CMAMMA)的临床表型及基因变异特征。方法 提取本例CMAMMA患儿及其父母外周血DNA,进行高通量测序技术检测变异基因,再进行Sanger测序验证。结果 患儿男性,4个月7d,发病早期临床症状轻重,表现为视觉传导通路延迟和智力测试边缘化,尿液检查结果显示甲基丙二酸MMA明显升高,丙二酸MA未升高。基因检测显示本例患儿为ACSF3基因突变c.259delG(p.C88Vfs*30)和c.1456G>A(p.A486T)的复合杂合子,前者来自于父亲,后者来自于母亲,均为新突变,且国内未见报道。结论 ACSF3基因位点中c.259delG(p.C88Vfs*30)的移码突变和c.1456G>A(p.A486T)的错义突变是导致该患儿CMAMMA致病因素。

Objective To investigate the clinical phenotype and gene variation of combined malonic acid methylmalonic aciduria(CMAMMA).Methods The peripheral blood DNA of this CMAMMA child and his parents was extracted,the mutant genes were detected by high-throughput sequencing technology,and then verified by sanger sequencing.Results The patient was male for 4 months and 7 days.The clinical manifestations were only delay of visual conduction pathway and marginalization of intelligence test.The results of urine examination showed that methylmalonic acid(MMA) was significantly increased,but malonic acid(MA) was not increased.Gene detection showed that this child was a compound heterozygote of ACSF3 gene mutation c.259 delG(p.C88 Vfs*30) and c.1456 G> A(p.A486 T).The former came from the father and the latter from the mother.Both of them were new mutations that had not been reported and were reported for the first time in China.Conclusion The frameshift mutation of c.259 delG(p.C88 Vfs*30) and the missense mutation of c.1456 G>A(p.A486 T) in ACSF3 gene locus are the pathogenic factors of CMAMMA in this child.