Tandem mass spectrometric enzyme assay for simultaneous detection of Tay-Sachs and Sandhoff diseases in dried blood spots for newborn screening

IF 3.7 2区生物学 Q2 ENDOCRINOLOGY & METABOLISM Molecular genetics and metabolism Pub Date : 2024-06-19 DOI:10.1016/j.ymgme.2024.108517

Zackary M. Herbst , Stephan Hold , Michael H. Gelb , Hamid Khaledi

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Abstract

GM2 gangliosidosis is a group of rare lysosomal storage disorders (LSDs) including Tay-Sachs disease (TSD) and Sandhoff disease (SD), caused by deficiency in activity of either β-hexosaminidase A (HexA) or both β-hexosaminidase A and β-hexosaminidase B (HexB). Methods for screening and diagnosis of TSD and SD include measurement and comparison of the activity of these two enzymes. Here we report a novel method for duplex screening of dried blood spots (DBS) for TSD and SD by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method requires incubation of a single 3 mm DBS punch with the assay cocktail followed by the injection into the LC-MS/MS. The performance of the method was evaluated by comparing the confirmed TSD and SD patient DBS to random healthy newborn DBS which showed easy discrimination between the three cohorts. The method is multiplexable with other LSD MS/MS enzyme assays which is critical to the continued expansion of the NBS panels.

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串联质谱酶测定法，用于同时检测新生儿筛查干血斑中的泰-萨克斯病和桑德霍夫病

GM2神经节苷脂病是一组罕见的溶酶体储积症（LSD），包括泰-萨克斯病（Tay-Sachs disease，TSD）和桑德霍夫病（Sandhoff disease，SD），由β-己糖胺酸酶A（HexA）或β-己糖胺酸酶A和β-己糖胺酸酶B（HexB）活性缺乏引起。筛查和诊断 TSD 和 SD 的方法包括测量和比较这两种酶的活性。在此，我们报告了一种通过液相色谱-串联质谱（LC-MS/MS）对干血斑（DBS）进行 TSD 和 SD 双重筛查的新方法。该方法需要将单个 3 mm DBS 冲孔与检测鸡尾酒孵育，然后注入 LC-MS/MS。通过将确诊的 TSD 和 SD 患者 DBS 与随机健康新生儿 DBS 进行比较，对该方法的性能进行了评估，结果显示这三种人群之间很容易区分。该方法可与其他 LSD MS/MS 酶测定法复用，这对继续扩大 NBS 面板至关重要。

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来源期刊

Molecular genetics and metabolism 生物-生化与分子生物学

CiteScore

5.90

自引率

7.90%

发文量

621

审稿时长

34 days

期刊介绍： Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.