A tandem mass spectrometry diagnostic test for newborn screening of Tay-Sachs and Sandhoff diseases

总结 本计画的目标是发展一种新生儿筛检的串联质谱分析法 GM 2-神经节苷脂沉积症，目前正在开发几种治疗方案。GM 2- 神经节苷脂沉积症包括泰-萨二氏病和桑德霍夫病， 会导致神经细胞逐渐退化泰-萨克斯病是由HexA酶引起的 山德霍夫病是由HexA和HexB酶缺乏引起的。的 这些疾病的发病率在全世界的某些人群中很高。比如说， 在德系犹太人中，泰-萨克斯病的发病率约为每3,500名新生儿中有1名 并且每29个个体中有1个携带者频率。山德霍夫病的携带者频率 从一般人群的1：310到隔离社区的1：7， 血缘关系在本项目中，一种同时检测泰-萨克斯和桑德霍夫的方法， 将开发适合新生儿筛查的疾病。一拳从干血斑（DBS） 新生儿筛查卡上的DNA用作酶（HexA和HexB）的来源。DBS将在 用含有两种合成底物（特异性HexA底物和特异性HexA底物）的混合物孵育， HexA/B底物），以允许形成两种酶产物，然后通过 串联质谱（MS/MS）。我们的方法只需要一次孵化， MS/MS进样。

Summary The goal of this project is to develop a tandem mass spectrometry assay for newborn screening of GM2-gangliosidosis for which several treatment options are being developed. GM2- gangliosidosis includes Tay-Sachs and Sandhoff diseases, inherited metabolic disorders which cause a progressive deterioration of nerve cells. Tay-Sachs disease is caused by HexA enzyme deficiency and Sandhoff disease is caused by deficiency of both HexA and HexB enzymes. The incidence of these disorders is high among certain populations around the world. For example, in the Ashkenazi Jewish population the Tay-Sachs incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. The carrier frequency of Sandhoff disease range from 1:310 in the general population to 1:7 in isolated communities with a high degree of consanguinity. In this project, a method for simultaneous detection of Tay-Sachs and Sandhoff disease suitable for newborn screening will be developed. A punch from a dried blood spot (DBS) on a newborn screening card is used as a source of the enzyme (HexA and HexB). DBS will be incubated with a cocktail containing two synthetic substrates (a specific HexA substrate and a HexA/B substrate) to allow formation of two enzymatic products which will be then quantified by tandem mass spectrometry (MS/MS). Our method would require one single incubation and one MS/MS injection.