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

用于新生儿泰萨克斯病和桑德霍夫病筛查的串联质谱诊断测试

• 批准号: 10484192
• 负责人: Michael H Gelb
• 金额: $ 23.32万
• 依托单位: GELBCHEM, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-08 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484192
• 关键词: Biological Assay; Birth; Blood; Businesses; Chemistry; Clinical; Communities; Consanguinity; Deficiency Diseases; Detection; Deterioration; Development; Diagnostic tests; Disease; Enzymes; Frequencies; Gangliosidoses GM2; General Population; Goals; Grant; Hand; Incidence; Incubated; Individual; Inherited; Injections; Laboratories; Life; Lysosomal Storage Diseases; Mass Spectrum Analysis; Metabolic Diseases; Methods; Neonatal Screening; Neurons; Newborn Infant; Patients; Population; Process; Reagent; Research; Sandhoff Disease; Series; Source; Spottings; Tay-Sachs Disease; Technology; Treatment outcome; Work; assay development; base; beta-n-acetylhexosaminidase; enzyme deficiency; follower of religion Jewish; improved; interest; prospective; tandem mass spectrometry; therapy development

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.

概括 该项目的目的是开发串联质谱法测定到新生儿筛查 GM2 - 胶状病的病正在开发几种治疗选择。 GM2- 神经节病包括Tay-Sachs和Sandhoff疾病，遗传的代谢性疾病 导致神经细胞的逐渐恶化。 Tay-Sachs病是由Hexa酶引起的 缺乏症和Sandhoff疾病是由HEXA和HEXB酶缺乏引起的。这 这些疾病的发病率很高。例如， 在Ashkenazi犹太人口中，Tay-Sachs发病率每3500名新生儿大约1个 每29个人中的载体频率为1。 Sandhoff病的载体频率 在一般人口中的1：310到高度的孤立社区的1：7 血缘。在这个项目中，一种同时检测Tay-Sachs和Sandhoff的方法 适合新生儿筛查的疾病将开发。干血点（DBS）的拳头 在新生儿筛选卡上被用作酶的来源（Hexa和HexB）。 DB会 与含有两个合成底物的鸡尾酒孵育（特定的HEXA底物和A hexa/b底物）允许形成两种酶促产品，然后将其量化 串联质谱法（MS/MS）。我们的方法需要一个单一的孵化和一个 MS/MS注射。