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

GC/MS 新生儿有机酸血症筛查的初步研究

基本信息

批准号：
10557077
负责人：
YAMAGUCHI Seiji
金额：
$ 1.15万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10557077/
关键词：
organic acid disorder defects of gluconeogenesis gas chromatography mass spectrometry mass screening stable isotope dilution analysis neonates child health 先天代謝異常 GC MS 国際協力

项目摘要

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.

新生儿有机酸血症筛查的重要性已在世界范围内得到认可。我们进行了基础研究，以简化、加快和提高GC/MS分析筛选的灵敏度。结果如下：1)自动GC/MS数据系统的建立：完成了GC/MS数据自动代谢谱分析和疾病检测的个人计算机辅助系统。2)尿滤纸GC/MS筛选：干燥的尿滤纸便于样品运输。我们考察了尿滤纸的实用性。25种化合物中的大多数在滤纸上至少稳定28天。我们分析了来自亚洲国家的600多份尿液滤纸样本，检测出41名有机酸血症患者。3)岛根县新生儿群体筛查的中试研究：对岛根县4005名新生儿进行了为期3年的新生儿群体筛查中试。其中发现1例高苯丙氨酸血症婴儿，筛查婴儿中有4.6%出现过性新生儿异常。4)用GC/MS筛选有机酸血症的研究：我们研究了用TBDMS-衍生法进行GC/MS分析，并与常用的三甲基硅基（TMS）衍生法进行了比较。TBDMS法具有较高的灵敏度和可靠性。5)干血滤纸游离脂肪酸的研究：建立了一种简便、灵敏的干血滤纸游离脂肪酸分析方法。我们证实了11例脂肪酸β -氧化障碍可以用这种方法识别。6)果糖- 1,6 -二磷酸酶（FDPase）缺乏症的简易筛查方法：我们建立了一种快速、简便、无创、灵敏的FDPase缺乏症检测方法，仅需少量尿液。对预防FDPase缺乏症患者因低血糖而猝死具有重要意义。