新生儿甲基丙二酸血症的筛查与基因突变分析

Screening and Gene Mutation Analysis of Neonatal Methylmalonic Acidemia

目的分析甲基丙二酸血症(methylmalonic acidemia),MMA的临床筛查、基因突变情况。方法采用串联质谱技术对新生儿疾病筛查中心的150 583例新生儿MMA进行筛查,并利用基因测序技术对其基因突变情况进行分析。结果确诊的18例MMA患儿中单纯型MMA 5例,合并型MMA 13例,经治疗后各生化指标均明显改善,8例检测出MMACHC基因突变,1例检测出HCFC1基因突变,1例同时存在这两种基因突变。随访6个月,3例单纯型MMA患儿中2例体格、智能均发育正常。8例合并型MMA患儿中5例生长发育正常,1例出现轻度精神运动发育迟缓。结论液相色谱串联质谱技术有助于早期筛查MMA,MMACHC基因缺陷是导致MMA的主要原因,且患儿预后与维生素B_(12)反应性、疾病类型等有关。

Objective To analyze the clinical screening and gene mutation of methylmalonic acidemia(MMA).Methods Tandem mass spectrometry was used to screen 150583 newborn MMA cases in the Neonatal Disease Screening Center,and their gene mutations were analyzed by gene sequencing technology.Results Among the 18 children diagnosed with MMA,5 were simple MMA and 13 were combined MMA.After treatment,the biochemical indicators were significantly improved.MMAHC gene mutation was detected in 8 cases,HCFC1 gene mutation was detected in 1 case,and HCFC1 gene mutation was detected in 1 case.There were mutations in both genes.During a 6-month follow-up,2 of the 3 children with simple MMA had normal physical and intellectual development.Of the 8 children with combined MMA,5 had normal growth and development,and 1 had mild psychomotor developmental delay.Conclusion Liquid chromatography tandem mass spectrometry technology is helpful for early screening of MMA.MMAHC gene defects are the main cause of MMA,and the prognosis of children is related to vitamin B_(12) responsiveness and disease types.