通过串联质谱法在干血斑（DBS）中检测黏多糖贮积症 III-A（Sanfilippo 综合征-A）。
Detection of mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in dried blood spots (DBS) by tandem mass spectrometry.
机构信息
Department of Chemistry, Bagley Hall, University of Washington, Box 351700, Seattle, Washington 98195-1700, United States.
University of Georgia's Complex Carbohydrate Research Center, 315 Riverbend Road, Athens, GA 30602, United States.
出版信息
Mol Genet Metab. 2018 Sep;125(1-2):59-63. doi: 10.1016/j.ymgme.2018.05.005. Epub 2018 May 23.
Abstract
BACKGROUND
With ongoing efforts to develop improved treatments for Sanfilippo Syndrome Type A (MPS-IIIA), a disease caused by the inability to degrade heparan sulfate in lysosomes, we sought to develop an enzymatic activity assay for the relevant enzyme, sulfamidase, that uses dried blood spots (DBS).
METHODS
We designed and synthesized a new sulfamidase substrate that can be used to measure sulfamidase activity in DBS using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS
Sulfamidase activity was readily detected in DBS using the new substrate and LC-MS/MS. Sulfamidase activity showed acceptable linearity proportional to the amount of enzyme and reaction time. Sulfamidase activity in 238 random newborns was well elevated compared to the range of activities measured in DBS from 8 patients previously confirmed to have MPS-IIIA.
CONCLUSIONS
This is the first report of an assay capable of detecting sulfamidase in DBS. The new assay could be useful in diagnosis and potentially for newborn screening of MPS-IIIA.
摘要
背景
随着开发 Sanfilippo 综合征 A 型（MPS-IIIA）改良治疗方法的持续努力，这种疾病是由于溶酶体中无法降解硫酸乙酰肝素引起的，我们试图开发一种使用干血斑（DBS）的相关酶——芳基硫酸酯酶的酶活性测定法。
方法
我们设计并合成了一种新的芳基硫酸酯酶底物，可用于使用液相色谱-串联质谱法（LC-MS/MS）测量 DBS 中的芳基硫酸酯酶活性。
结果
使用新的底物和 LC-MS/MS 可以很容易地在 DBS 中检测到芳基硫酸酯酶活性。芳基硫酸酯酶活性与酶的量和反应时间呈比例，具有可接受的线性关系。与先前确认患有 MPS-IIIA 的 8 名患者的 DBS 中测量的活性范围相比，238 名随机新生儿的芳基硫酸酯酶活性明显升高。
结论
这是首次报道能够在 DBS 中检测芳基硫酸酯酶的测定法。新的测定法可用于 MPS-IIIA 的诊断和潜在的新生儿筛查。
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