串联质谱和高效液相色谱-串联质谱二次筛查联合应用于新生儿MMA筛查

目的探讨串联质谱和高效液相色谱-串联质谱二次筛查联合应用在甲基丙二酸血症(MMA)中的筛查价值。方法收集新生儿串联质谱初筛结果中C3、C3/C2、C3/C0单一或多个指标异常的新生儿干血滤纸片标本,用高效液相色谱-串联质谱的方法定量检测原始血片中甲基丙二酸、甲基枸橼酸和高半胱氨酸,对二次筛查后疑似阳性的新生儿进行召回复查,并进行尿气相色谱/质谱检测。临床诊断患儿进一步予以基因检测进行确诊。结果共收集423例C3、C3/C2、C3/C0单一或多个指标异常的新生儿筛查标本,初筛阳性率约为1%,行联合筛查检测结果发现8例标本中甲基丙二酸和同型半胱氨酸表达水平明显升高,召回复查尿气相色谱质谱提示甲基丙二酸轻度升高。结论串联质谱和高效液相色谱-串联质谱联合应用可以提高新生儿MMA筛查的阳性预测值、降低假阳性率,在新生儿遗传代谢病筛查中具有重要价值。

Combined application of MS/MS and LC-MS/MS in the newborn screening of children with methylmalonic acidemia

Abstract:Objective: To investigate the combined application value of tandem mass spectrometry (MS/MS) and high performance liquid chromatogram-tandem mass spectrometry (LC-MS/MS) in the newborn screening of children with methylmalonic acidemia (MMA). Methods: The dried blood spot samples from the newborn with abnormal propionylcarnitine (C3) or C3/acetylcarnitine (C2) or C3/free carnitine (C0) levels in the preliminary screening of MS/MS were collected, and the concentrations of MMA, methylcitric acid (MCA) and homocysteine (Hcy) in these samples were detected with LC-MS/MS. The neonates with increased MMA, MCA or Hcy levels were recalled, and their urinary organic acids were analyzed with gas chromatographic mass spectrometry (GC/MS). Last, gene mutation analysis was performed to make a definite diagnosis. Results: A total of 423 samples with abnormal C3 or C3/C2 or C3/C0 levels in the newborn screening were collected, and the positive rate of preliminary screening was about 1%. The LC-MS/MS results showed that 8 neonates had higher MMA and tHcy levels. The GC/MS results further showed that the level of MMA increased slightly. Conclusion: The combined application of MS/MS and LC-MS/MS may increase the positive predictive value and decrease the false positive rate of MMA screening in the newborn, which may have an important clinical significane in the screening of inherited metabolic disorders.