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

气相色谱/质谱法在临床检验医学，特别是有机酸中毒的化学诊断中越来越受欢迎。然而，在日本，GC/MS的普及程度还不够，可能是由于GC/MS设备的维护困难或GC/MS数据的解释困难，也可能是由于对遗传代谢疾病的知识要求。我们开发了一个使用个人电脑的自动GC/MS数据分析和疾病检测系统，并在以下实验室测试中证实了它的实用性。1)标准有机酸血症筛查：尿液有机酸的溶剂萃取是有机酸血症筛查最常用的制备方法。提前登记了诊断所需的约120种尿液代谢物。经过溶剂萃取和GC/MS分析，我们确认数据可以自动处理和分析尿液代谢物，并且可以在个人计算机上进行可能的诊断。2)新生儿全面群体筛查：制备过程中，尿样直接干燥衍生。样品的制备使氨基酸、碳水化合物或其他物质以及有机酸的分析成为可能。我们将该系统用于筛选方法，并证实该系统可以自动分析这些预设化合物的GC/MS数据并成功诊断疾病。3)稳定同位素稀释分析：稳定同位素稀释法是一种灵敏度极高的GC/MS分析方法，尤其适用于量过小的代谢物。我们将该系统应用于稳定同位素法测定尿酰基甘氨酸，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.