Development of automated GC/MS data profiling and disease-detection sytems for organic acidemia screening.

GC/MS在临床检验医学，特别是有机酸中毒的化学诊断中正变得越来越流行。然而，在日本，GC/MS目前仍然不够普及，可能是由于GC/MS设备的维护或GC/MS数据解释的困难，或者是对遗传性代谢紊乱知识的要求。我们利用一台个人计算机开发了一套自动化的GC/MS数据图谱和疾病检测系统，并在以下实验室测试中证实了其有效性：1)标准有机酸血症筛查：有机酸血症筛查最常用的制备方法是尿有机酸的溶剂萃取法。预先登记了诊断所需的大约120种尿代谢物。经过溶剂提取和GC/MS分析，我们确认数据可以自动处理和分析尿代谢物，并在个人计算机上通过该系统做出可能的诊断。2)全面的新生儿群体筛查：在准备过程中，尿样直接干涸和衍生化。样品的制备使氨基酸、碳水化合物或其他以及有机酸的分析成为可能。3)稳定同位素稀释法：稳定同位素稀释法是一种非常灵敏的GC/MS分析方法，特别是对于含量太少的代谢物。我们将该系统应用于稳定同位素法检测尿酰甘氨酸，设置了多个内标，证实了该系统的实用性。

GC/MS is becoming popular for clinical laboratory medicine, in particular, chemical diagnosis of organic acidemias. In Japan, however, GC/MS is not enough popular still now, probably because of difficulties in maintenance of GC/MS equipments or GC/MS data interpretation, or requirements of knowledge on the inherited metabolic disorders. We developed an automated GC/MS data profiling and disease detection system using a personal computer, and confirmed its usefulness in the following laboratory tests.1) Standard organic acidemia screening : The solvent extraction of urinary organic acids is a most popular preparation method for organic acidemia screening. About 120 kinds of urinary metabolites that are necessary for the diagnosis were enrolled in advance. We confirmed after the solvent extraction and GC/MS analysis that the data could be automatically processed and profiled urinary metabolites, and that the possible diagnosis was made by this system on a personal computer.2) Comprehensive neonatal mass screening : In preparation, urinary samples were directly dried up and derivatized. Preparation of the samples enable the analysis of amino acids, carbohydrates or others as well as organic acids. We apllied this system for the screening method and confirmed that this system could automatedly profile GC/MS data of these compounds preset and successfully diagnose the diseases.3) Stable isotope dilution analysis : The stable isotope dilution method is an extremely sensitive GC/MS analytical method, in particular, for metabolites whose amount is too small. We applied this system to the stable isotope method to determine urinary acylglycines, setting multiple internal standards, and confirmed the usefulness of this system.