超高效液相色谱-串联质谱血液代谢物检测在甲基丙二酸血症筛查与监测中的应用

Application of blood metabolites by determination ultra-high performance liquid chromatography-tandem mass spectrometry in screening and monitoring of methylmalonic acidemia

目的探讨超高效液相色谱-串联质谱法(二阶筛查串联质谱法)在甲基丙二酸血症(methylmalonic acidemia,MMA)筛查与患儿随访检测中的应用价值,并分析与传统串联质谱法、尿气相色谱质谱法检测MMA各指标的相关性。方法收集济南市妇幼保健院新生儿疾病筛查中心2021年2月至2022年1月49490名新生儿干血滤纸片,初筛丙酰肉碱(propionycarnitine,C3),及其与乙酰肉碱(acetylcarnitine,C2)比值C3/C2任一指标异常的样本进行二阶筛查;分析定期随访治疗的MMA患儿二阶筛查串联质谱法、传统串联质谱法及尿气相色谱质谱法检测各指标浓度变化及其相关性。结果49490名新生儿传统串联质谱法MMA筛查阳性500例,筛查阳性率1.01%(500/49490),基因检测确诊16例;进入二阶筛查串联质谱检测流程样本827例,阳性31例,筛查阳性率0.06%(31/49490),基因检测确诊16例,与传统串联质谱法确诊样本相符。二阶筛查串联质谱法与血清同型半胱氨酸、传统串联质谱法及尿气相色谱质谱法检测各指标均存在正相关性(P<0.05)。结论MMA二阶筛查串联质谱法筛查阳性率明显低于传统串联质谱法,其与传统串联质谱法、尿气相色谱质谱法联合检测,可有效提高MMA筛查诊断效率,并可用于患儿疗效观测,开展更有针对性的治疗。

Objective To investigate the application value of ultra-performance liquid chromatography-tandem mass spectrometry by second-order screening method in methylmalonic acidemia(MMA)screening and follow-up detection of positive children,and analyze the its correlation with traditional tandem mass spectrometry screening method and gas chromatography-mass spectrometry(GC-MS)in the detection of MMA indicators.Methods A total of 49,490 neonatal dried blood filter paper samples with abnormal propionyl carnitine(C3)or abnormal ration between C3 acetylcarnitine(C2)were collected for second-order screening.Analyze the changes of the concentration of each index detected by the second order screening,tandem mass spectrometry and urinary organic acid spectrum and the correlation in the children with MMA who were followed up regularly.Results Among 49490 newborns,500 samples were positive for MMA screening by traditional tandem mass spectrometry,with a positive rate of 1.01%,and 16 samples were confirmed by gene testing.Of the 827 samples that entered the second-stage screening process,31 samples were positive,the screening positive rate was 0.06%,and 16 samples were confirmed by gene testing,which was consistent with the confirmed samples by traditional tandem mass spectrometry.There was a positive correlation between the second order screening and serum homocysteine,traditional tandem mass spectrometry and urine organic acid spectrum in the detection of various indicatiors(P<0.05).Conclusion The positive rate of MMA screening by the second-order screening method is significantly lower than that by the traditional tandem mass spectrometry.The combined detection of the second-order screening method is the traditional tandem mass spectrometry and urinary organic acid spectrometry can effectively improve the diagnostic efficiency of MMA screening,and can be used to observe the efficacy in children in order to carry out more targeted treatment.