新生儿甲基丙二酸血症筛查及随访分析

Screening and follow-up analysis of neonatal methylmalonic acidemia

目的了解淄博市新生儿甲基丙二酸血症(MMA)的总体发病率,分析MMA合并型临床特征、基因突变特点及预后。方法通过串联质谱技术筛查本市2013年10月至2019年7月出生且监护人自愿选择筛查的所有新生儿样本,对诊断为MMA的新生儿进行基因检测。结果筛查185239例新生儿中共确诊44例,单纯型5例,合并型39例;39例合并型治疗随访时间9 d~6.5岁不等,新生儿期死亡3例,27例无症状,9例有症状,表现为不同程度的眼球震颤、癫痫、脑积水和智能发育落后等;血液同型半胱氨酸浓度与尿中MMA浓度Spearman相关分析P=0.474。MMACHC基因检测突变位点检出率100.00%,检出16种突变类型,携带c.482G>A基因的患儿预后好;死亡病例分别携带c.609G>A/c.80A>G;c.80A>G纯合突变;c.277-3_303del/c.658_660del AAG。结论淄博市甲基丙二酸血症发病率为1/4210,合并型甲基丙二酸血症基因型与表型相关,同型半胱氨酸浓度升高与预后相关,与尿中MMA浓度无密切相关。早诊断、早期规范治疗预后好。

Objective To investigate the overall incidence of neonatal methylmalonic academia(MMA)in Zibo city,and to analyze the clinical characteristics,gene mutation characteristics and prognosis of combined MMA.Methods Tandem mass spectrometry was used to screen all newborns born from October 2013 to July 2019 in the city whose guardians voluntarily selected screening.Genetic testing was performed on newborns diagnosed with MMA.Results Among the 185239 newborns screened,there were 44 newborns diagnosed with MMA,including 5 with simple MMA and 39 with combined MMA.In the 39 newborns with combined MMA,the follow-up time ranged from 9 days to 6.5 years.There were 3 newborns died in neonatal period,27 asymptomatic newborns,and 9 symptomatic newborns,manifested as varying degrees of nystagmus,epilepsy,hydrocephalus,and mental retardation.Spearman correlation analysis of blood homocysteine concentration and urine MMA concentration showed P=0.474.The detection rate of mutation sites in MMACHC gene detection was 100.00%,and 16 mutation types were detected.Children with c.482G>A gene had a good prognosis.Dead newborns carried c.609G>A/c.80A>G,c.80A>G homozygous mutation,and c.277-3_303del/c.658_660del AAG.Conclusion The incidence of MMA in Zibo city is 1/4210.The genotype of combined MMA is related to the phenotype.The increase of homocysteine concentration is related to the prognosis,and it is not closely related to the urine MMA concentration.Early diagnosis and early standard treatment promise good prognosis.