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

总结 该项目的目标是开发一种用于新生儿筛查的串联质谱分析方法 GM2-神经节苷脂沉积症的几种治疗方案正在开发中。 GM2- 神经节苷脂贮积症包括泰-萨克斯病和桑德霍夫病，遗传性代谢紊乱， 导致神经细胞逐渐退化。泰萨克斯病是由 HexA 酶引起的 缺乏症和桑德霍夫病是由 HexA 和 HexB 酶缺乏引起的。的 这些疾病在世界各地的某些人群中发病率很高。例如， 在德系犹太人口中，泰萨克斯病的发病率约为每 3,500 名新生儿中就有 1 人 携带频率为每29个人中就有1个。桑德霍夫病的携带频率 范围从一般人群的 1:310 到高程度隔离社区的 1:7 血缘关系。在这个项目中，一种同时检测 Tay-Sachs 和 Sandhoff 的方法 将开发出适合新生儿筛查的疾病。来自干血点的一拳（DBS） 新生儿筛查卡上的酶被用作酶的来源（HexA 和 HexB）。星展银行将 与含有两种合成底物（一种特定的 HexA 底物和一种 HexA/B 底物）以允许形成两种酶产物，然后通过以下方式对其进行定量 串联质谱 (MS/MS)。我们的方法需要一次孵化和一次 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.