Laboratory of Inherited Metabolic Disorders and Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Tř. Svobody 8, 771 26 Olomouc, Czech Republic.
J Chromatogr A. 2012 Feb 24;1226:11-7. doi: 10.1016/j.chroma.2011.09.074. Epub 2011 Oct 4.
Metabolomics has become an important tool in clinical research and diagnosis of human diseases. In this work we focused on the diagnosis of inherited metabolic disorders (IMDs) in plasma samples using a targeted metabolomic approach. The plasma samples were analyzed with the flow injection analysis method. All the experiments were performed on a QTRAP 5500 tandem mass spectrometer (AB SCIEX, U.S.A.) with electrospray ionization. The compounds were measured in a multiple reaction monitoring mode. We analyzed 50 control samples and 34 samples with defects in amino acid metabolism (phenylketonuria, maple syrup urine disease, tyrosinemia I, argininemia, homocystinuria, carbamoyl phosphate synthetase deficiency, ornithine transcarbamylase deficiency, nonketotic hyperglycinemia), organic acidurias (methylmalonic aciduria, propionic aciduria, glutaric aciduria I, 3-hydroxy-3-methylglutaric aciduria, isovaleric aciduria), and mitochondrial defects (medium-chain acyl-coenzyme A dehydrogenase deficiency, carnitine palmitoyltransferase II deficiency). The controls were distinguished from the patient samples by principal component analysis and hierarchical clustering. Approximately 80% of patients were clearly detected by absolute metabolite concentrations, the sum of variance for first two principle components was in the range of 44-55%. Other patient samples were assigned due to the characteristic ratio of metabolites (the sum of variance for first two principle components 77 and 83%). This study has revealed that targeted metabolomic tools with automated and unsupervised processing can be applied for the diagnosis of various IMDs.
代谢组学已成为人类疾病临床研究和诊断的重要工具。在这项工作中，我们专注于使用靶向代谢组学方法诊断血浆样本中的遗传性代谢紊乱（IMD）。使用流动注射分析方法对血浆样本进行分析。所有实验均在 AB SCIEX（美国）的 QTRAP 5500 串联质谱仪上进行，采用电喷雾电离。以多重反应监测模式测量化合物。我们分析了 50 个对照样本和 34 个氨基酸代谢缺陷样本（苯丙酮尿症、枫糖尿症、酪氨酸血症 I、精氨酸血症、高胱氨酸尿症、氨甲酰磷酸合成酶缺乏症、鸟氨酸转氨甲酰酶缺乏症、非酮性高甘氨酸血症）、有机酸尿症（甲基丙二酸尿症、丙酸血症、戊二酸血症 I、3-羟基-3-甲基戊二酸尿症、异戊酸血症）和线粒体缺陷（中链酰基辅酶 A 脱氢酶缺乏症、肉碱棕榈酰转移酶 II 缺乏症）。通过主成分分析和层次聚类，对照样本与患者样本区分开来。大约 80%的患者通过绝对代谢物浓度明显被检测到，前两个主成分的方差总和在 44-55%范围内。其他患者样本则由于代谢物的特征比（前两个主成分的方差总和为 77 和 83%）被分配。本研究表明，具有自动化和无监督处理的靶向代谢组学工具可应用于各种 IMD 的诊断。
