Research for accuracy in disease detection and medical intervention in newborn screening system using tandem mass spectrometry

串联质谱新生儿筛查系统疾病检测和医疗干预准确性研究

• 批准号: 14570731
• 负责人: SHIGEMATSU Yosuke
• 金额: $ 2.24万
• 依托单位: Faculty of Medical Sciences, University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570731/
• 关键词: newborn screening; carnitine; tandem mass spectrometry; inborn errors of metabolism; amino acid; organic acid; fatty acid oxidation; sudden death in infancy

The subjects in newborn screening pilot study using tandem mass spectrometry were investigated in order to establish the practical screening system in Japan.The tentative cutoff values were tested using the dried blood spots of the patients with target disorders in this project, such as multiple acyl-CoA dehydrogenation defect (GA-II), medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, very-long-chain aryl-CoA dehydrogenase deficiency, and multiple carboxylase deficiency. The ratios of propionylcarnitine to acetylcarnitine were shown to be better marker for the screening of propionic academia and calssical methylmalonic aciduria.The severity of the diseases in patients found in this screening were estimated by the measurement of enzyme activities and the analysis of DNA mutation, which were done in cooperation with the researchers in Hiroshima University and Kyoto University. Therapies for the patients were conducted based on the results in this categories, and almost all patients, except for those with the severest form of the disease, are in good condition.The methods were modified using rust-free N2 drier and less expensive reagent to improve the sample quality and cost burden.We have analyzed about 200,000 dried blood spots and found 25 patients, which enable us to estimate the frequency of target diseases in Japan. In Japan, organic acidemias, such as propionic acidemia and glutaric aciduia type I, are relatively common, and fatty acid oxidation disorders, such as MCAD defiency and GA-II, are not so rare as believed before. It is suggested that screening system in Japan, including medical care for the patients, should be modified for such target diseases.

为了在日本建立实用的筛查系统，对使用串联质谱法进行新生儿筛查初步研究的受试者进行了调查。使用该项目中目标疾病患者的干血斑测试了暂定截止值，如多重酰基辅酶A脱氢酶缺陷（GA-II）、中链酰基辅酶A脱氢酶缺陷（MCAD）、极长链芳基辅酶A脱氢酶缺陷、和多种羧化酶缺乏症。丙酰肉毒碱与乙酰肉毒碱的比值是筛选丙酸尿症和甲基丙二酸尿症的较好指标，本研究与广岛大学和京都大学的研究人员合作，通过测定酶活性和分析DNA突变来估计筛选中发现的患者的疾病严重程度。根据这类结果对病人进行治疗，除最严重的病人外，几乎所有病人的情况都很好。我们改进了方法，使用了无锈的N2干燥剂和较便宜的试剂，以提高样品质量和费用负担。我们分析了约20万个干血斑，发现25例病人，这使我们能够估计日本目标疾病的频率。在日本，有机酸血症，如丙酸血症和I型谷氨酸血症，是相对常见的，脂肪酸氧化障碍，如MCAD缺乏症和GA-II，并不像以前认为的那样罕见。建议日本的筛查系统，包括对患者的医疗护理，应针对这些目标疾病进行修改。

项目成果

但馬剛: "高速液体クロマトグラフィ法による有機酸・脂肪酸代謝異常症の酵素診断"日本マススクリーニング学会誌. 13(1). 39-45 (2003)

Tsuyoshi Tajima：“使用高效液相色谱法进行有机酸/脂肪酸代谢紊乱的酶诊断”，日本大众筛查学会杂志 13(1) (2003)。

Shigematsu Y: "Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan"J Chromatogr B. 776(1). 39-48 (2002)

Shigematsu Y：“日本使用电喷雾串联质谱法进行新生儿大规模筛查和选择性筛查”J Chromatogr B. 776(1)。

Yorifuji T: "Unexpectedly high prevalence of the mild form of propionic acidemiain Japan : presence of a common mutation and possible clinical implications."Hum Genet. 112(2). 161-165 (2002)

Yorifuji T：“日本轻度丙酸血症的患病率出人意料地高：存在常见突变和可能的临床影响。”Hum Genet。

Fukao T, Zhang GX, Sakura N, Kubo T, Yamaga H, Hazama A, Kohno Y, Matsuo N, Kondo M, Yamaguchi S, Shigematsu A, Kondo N: "The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients : urinary organic acid and blood acylcarnitine profie

Fukao T、Zhang GX、Sakura N、Kubo T、Yamaga H、Hazama A、Kohno Y、Matsuo N、Kondo M、Yamaguchi S、Shigematsu A、Kondo N：“日本患者的线粒体乙酰乙酰辅酶A硫解酶 (T2) 缺乏症

Shigematsu Y, Hirano S, Hata I, Tanaka Y, Sudo M, Sakura N, Tajima T, Yamaguchi S.: "Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan."J Chromatogr B. 776. 39-48 (2002)

Shigematsu Y、Hirano S、Hata I、Tanaka Y、Sudo M、Sakura N、Tajima T、Yamaguchi S.：“日本使用电喷雾串联质谱法进行新生儿大规模筛查和选择性筛查。”J Chromatogr B. 776. 39-48