Campos H Derbis
Departamento de Genética Bioquímica, Campus del ICBP Victoria de Girón, Centro Nacional de Genética Médica, La Habana, Cuba.
Rev Med Chil. 2011 Oct;139(10):1356-64. Epub 2012 Jan 3.
The use of tandem mass spectrometry for the diagnosis of inborn errors of metabolism has the potential to expand the newborn screening panel to include a vast number of diseases. This technology allows the detection, in the same spot of dried blood on filter paper and during one single analytical run, of different metabolic diseases. Tandem mass spectrometry is rapidly replacing the classical screening techniques approach of one-metabolite detected per analysis per disease by its ability of simultaneous quantification of several metabolites as markers of many diseases, such as acylcarnitines and amino acids. It is clear that a single metabolite can be a biomarker for several diseases, so the multiplex approach of using tandem mass spectrometry enhances, on average, the sensitivity and specificity of the screening. However, there are differences for particular metabolites and the diseases they detect within the same method. Disorders such as the tyrosinemias and among the organic acidemias, the methylmalonic acidemias, have a substantially higher false-positive rate than other more common metabolic diseases such as medium-chain acyl-CoA dehydrogenase deficiency and phenylketonuria. Before introducing this technology into routine newborn screening programs it is necessary to consider the frequency of each disease, as well as the response to early treatment or variables related to the collection of the sample.
串联质谱法用于先天性代谢缺陷的诊断，有可能扩大新生儿筛查项目，使其涵盖大量疾病。这项技术能够在滤纸干血斑的同一位置，通过单次分析检测出不同的代谢疾病。串联质谱法正迅速取代传统的筛查技术，传统技术每次分析只能检测一种疾病的一种代谢物，而串联质谱法能够同时对多种代谢物进行定量分析，这些代谢物可作为多种疾病的标志物，如酰基肉碱和氨基酸。显然，单一代谢物可能是多种疾病的生物标志物，因此使用串联质谱法的多重检测方法平均提高了筛查的灵敏度和特异性。然而，在同一检测方法中，特定代谢物及其所检测的疾病之间存在差异。诸如酪氨酸血症以及有机酸血症中的甲基丙二酸血症等疾病，其假阳性率比其他更常见的代谢疾病（如中链酰基辅酶A脱氢酶缺乏症和苯丙酮尿症）要高得多。在将这项技术引入常规新生儿筛查项目之前，有必要考虑每种疾病的发病率，以及对早期治疗的反应或与样本采集相关的变量。
