UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses
UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses
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DOI：
10.1016/j.aca.2016.06.054
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发表时间：
2016-09-14
影响因子：
6.2
通讯作者：
Clarke, Joe T. R.
中科院分区：
文献类型：
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作者：
Auray-Blais, Christiane;Lavoie, Pamela;Clarke, Joe T. R.
粘多糖沉积症（MPS）是一组由参与糖胺聚糖（GAG）降解的溶酶体酶的原发性缺陷引起的疾病。根据特定的酶缺陷，一种或多种GAG的催化剂被阻断，导致在组织和生物体液中积累。GAG测量对于高风险筛查、诊断、监测治疗疗效和患者随访非常重要。大多数生化遗传学实验室常用的二甲基亚甲蓝（DMB）分光光度法依赖于非特异性总GAG分析，这导致假阳性结果，甚至假阴性结果（主要用于MPS III和IV患者）。我们项目的主要目的是设计和验证一种可靠的串联质谱多重分析，用于尿液定量四种GAG（硫酸皮肤素（DS），硫酸乙酰肝素（HS），硫酸角质素（KS）和硫酸软骨素（CS）），最终将技术转移到临床。所开发的方法是快速的（7分钟），我们的结果显示良好的日内和日间精密度（RSD 0.995）的DS，HS，CS和KS校准曲线。与DMB分光光度法相比，该多重串联质谱法允许GAG分级分离，从而区分MPS类型，但MPS I和II除外，其特征在于具有相同的GAG谱。设计的方法是一个有用的和可靠的工具，MPS患者的诊断，以及他们的监测和随访，如纵向研究所示。(C)© 2016 Elsevier B.V.版权所有。
Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies. (C) 2016 Elsevier B.V. All rights reserved.