Preliminary studies on neonatal mass screening for organic acidemias using GC/MS

新生儿有机酸筛查的重要性已得到世界各国的认可。我们进行了基础研究，以简化，加快和提高灵敏度的GC/MS分析的筛选。结果如下：1）建立了GC/MS数据自动化系统，完成了GC/MS数据自动化分析和异常检测的计算机辅助系统。2）尿滤纸GC/MS筛查：干燥尿滤纸便于样品运输。我们研究了尿液滤纸的实用性。测试的25种化合物中的大多数在滤纸上稳定至少28天。我们分析了来自亚洲国家的600多份尿滤纸样本，并检测出41例有机酸血症患者。3）在岛根地区使用GC/MS进行新生儿筛查的试点研究：我们对岛根地区出生的4005名婴儿进行了为期3年的新生儿筛查试点。4）叔丁基二甲基硅基（TBDMS）衍生法在有机酸血症筛查中的应用研究：研究了TBDMS衍生法在有机酸血症筛查中的应用，并与最常用的三甲基硅基（TMS）衍生法进行了比较。TBDMS法更灵敏、可靠。5）干血滤纸中游离脂肪酸的研究：建立了一种简便、灵敏的干血滤纸中游离脂肪酸的分析方法。6）果糖-1，6-二磷酸酶缺乏症的简易筛查方法：建立了一种快速、简便、无创、敏感的检测果糖-1，6-二磷酸酶缺乏症的方法。对预防FDG缺乏者因低血糖而猝死有一定的意义。

Importance of the neonatal mass screening for organic acidemias has been recognized worldwide. We performed basic studies to simplify, speed up and raise the sensitivity of GC/MS analysis for the screening. The results were as follows :1) Establishment of an automated GC/MS data system : A personal computer-assisted system for automated metabolic profiling of GC/MS data and detection of disoorders was completed.2) GC/MS screening using urine filter paper : Dried urine filter paper is convenient for sample transport. We investigated the practicality of the urine filter paper. Most of 25 compounds tested were stable on the filter paper for at least 28 days. We analyzed over 600 samples of urine filter paper samples sent from Asian countries, and detected 41 organic acidemia patients.3) A pilot study of neonatal mass screening using GC/MS in the Shimane area : We perfromed a pilot neonatal mass screening for 4005 babies born in the Shimane area for 3 years. Among them, a baby with hyperphenylalaninemia was found, and transient neonatal abnoprmality was detected in 4.6% of babies screened.4) Study of t-butyldimethylsilyl (TBDMS)-derivatization in organic acidemia screening using GC/MS : We studied TBDMS-derivatization method for GC/MS analysis and compared with trimethylsilyl (TMS)-derivatization, a most popularmethod. The TBDMS method was more sensitive and reliable.5) Study of free fatty acids in dried blood filter paper : We established a simplified, sensitive method for analysis of free fatty acids in dried blood filter paper. We confirmed that 11 cases of fatty acid beta-oxidation disorders coud be identified by this method.6) Simplified screening method for detection of fructose-1, 6-diphosphatase (FDPase) deficiency : We established arapid, simplified, non-invasive and sensitive method to detect FDPase deficiency, using only a small amount of urine. It will be useful in prevention of sudeden death because of hypoglycemia in FDPase deficiency.