应用串联质谱技术进行河南省新生儿甲基丙二酸血症的筛查结果分析

Analysis of screening results of mass spectrometry-mass spectrometry for neonatal methylmalonic academia in Henan Province

目的探讨串联质谱技术(MS/MS)在河南省新生儿甲基丙二酸血症(MMA)筛查中的作用和意义,统计并了解我省MMA的发病情况。方法收集2012年12月至2018年12月的河南省出生72h后经充分哺乳的新生儿820 337例,采足跟血,制成干燥血滤纸片,MS/MS法检测血片丙酰基肉碱(C3)、游离肉碱(C0)、乙酰基肉碱(C2)、蛋氨酸(MET)、C3/C2、C3/C0、C3/MET。尿GC-MS检测尿液甲基丙二酸(MMA)、3-羟基丙酸、甲基枸橼酸的水平变化,结合血同型半胱氨酸(HCY)及基因检测以明确诊断。结果新筛共确诊174例MMA。其MS/MS结果显示C3增高的有144例,C3/C2增高的有171例。C3/MET增高的有148例。C3正常的为30例。尿MMA增高的有174例,甲基枸橼酸增高的有104例,3-羟基丙酸增高的有69例。HCY增高的有156例。基因检测显示156例为MMACHC型,即为B12有效型,其中c.609G>A突变出现频率最高。18例为MUT型,为B12无效型,其中c.1663G>A突变出现频率最高。结论 MMA是河南省新生儿遗传代谢病筛查中最常见的有机酸血症,其发病率为1/4714。且血C3/C2及尿MMA增高,对诊断MMA更具有特异性。MMA大部分为B12有效型,且MMACHC型MMA是MMA中最主要的类型,C3/MET和HCY的增高可以很好的提示MMA的基因分型为MMACHC型。通过MSMS筛查,多数患儿在无症状前就能被筛查出来,且可以在基因结果出来之前即可进行有效的治疗,是提高患者存活率和治疗效果的有效途径。

Objective:To investigate the role and significance of mass spectrometry-mass spectrometry(MS/MS)in the screening of neonatal methylmalonate(MMA)in Henan Province,and to make statistics and understand the incidence of MMA.Methods:From December 2012 to December 2018,820 337 cases of newborns in Henan province who were fully breast-fed 72 hours after birth were collected and treated with sufficient heel blood to make dry blood filter papers. They were tested by MSMS for propionyl carnitine(C3),free carnitine(C0),acetyl carnitine(C2),methionine(MET),C3/C2,C3/C0 and C3/MET. Urine GC-MS was used to detect the changes in urine levels of MMA,3-hydroxypropionic acid and methylcitric acid. Blood homocysteine and gene detection were also combined to make the diagnosis. Results:A total of 174 cases of MMA were confirmed.The results of MS/MS showed that there were 144 cases with increased C3 and 171 cases with increased C3/C2. There were 148 cases of increased C3/MET. C3 normal cases were 30. There were 174 cases of increased urinary MMA,104 cases of increased methylcitric acid,and 69 cases of increased 3-hydroxypropionic acid. There were 156 cases of increased homocysteine(HCY).Genetic testing showed that 156 cases were MMACHC type,that is,B12 effective type,of which the mutation frequency of609 G>A was the highest. 18 cases were MUT type and B12 invalid type,among which the mutation frequency of c.1663 G>A was the highest. Conclusion:MMA is the most common organic acidemia in newborn genetic metabolic disease screening in Henan Province,with the incidence of 1/4714. Blood C3/C2 and urine MMA increased,which is more specific for the diagnosis of MMA.Most of MMA is B12 effective type,and MMACHC type is the most important type of MMA. The increase of C3/MET and HCY can well indicate that the genotype of MMA is MMACHC type. Through MSMS screening,most children can be screened out before no symptoms,and can be effectively treated before the genetic results,which is an effective way to improve the survival rate and treatment effect of patients.