Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke , 3001, 12th Avenue North, Sherbrooke , Quebec, Canada J1H 5N4.
Anal Chem. 2013 Oct 1;85(19):9039-48. doi: 10.1021/ac401542k. Epub 2013 Sep 11.
Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A, which results in the progressive accumulation of glycosphingolipids. In addition to the two biomarkers, globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), which are routinely used for detection and high-risk screening of Fabry disease patients, novel urinary Gb3-related isoforms/analogues as well as newly defined lyso-Gb3 analogues in plasma and urine from Fabry patients have recently been described by our group. The aim of this study was to extend our recent analyses to identify and evaluate new potential Gb3-related biomarkers in the plasma of untreated male Fabry disease patients using a mass spectrometry metabolomic approach. A multivariate statistical analysis revealed five Gb3-related novel biomarkers in the plasma of male Fabry patients. Three of these new biomarkers correspond to Gb3, which has an extra double bond on the sphingosine with C16:0, C18:0, and C22:1 fatty acid chains. The fourth biomarker corresponds to a mixture of two structural isomers, the first with a d16:1 sphingosine and a C16:0 fatty acid and the second with a d18:1 sphingosine and a C14:0 fatty acid. To our knowledge, it is the first time that a Gb3 analogue with a d16:1 sphingosine moiety has been reported. In addition, this Gb3 analogue was also present in its methylated form. These biomarkers are part of a metabolic profile that may provide insight into the pathophysiology of Fabry disease.
法布里病是一种 X 连锁溶酶体贮积症，由α-半乳糖苷酶 A 缺乏引起，导致糖鞘脂的进行性积累。除了常规用于法布里病患者检测和高危筛查的两种生物标志物——神经酰胺三己糖苷（Gb3）和神经酰胺三己糖苷（lyso-Gb3）外，我们小组最近还描述了法布里病患者血浆中新的尿 Gb3 相关同工型/类似物以及新定义的 lyso-Gb3 类似物。本研究旨在扩展我们最近的分析，使用质谱代谢组学方法鉴定和评估未经治疗的男性法布里病患者血浆中的新潜在 Gb3 相关生物标志物。多变量统计分析显示，男性法布里病患者血浆中有 5 种 Gb3 相关的新生物标志物。其中 3 种新生物标志物与 Gb3 相对应，Gb3 在神经酰胺上有一个额外的双键，其脂肪酸链为 C16:0、C18:0 和 C22:1。第四个生物标志物对应于两种结构异构体的混合物，第一个异构体具有 d16:1 神经酰胺和 C16:0 脂肪酸，第二个异构体具有 d18:1 神经酰胺和 C14:0 脂肪酸。据我们所知，这是首次报道具有 d16:1 神经酰胺部分的 Gb3 类似物。此外，这种 Gb3 类似物也以其甲基化形式存在。这些生物标志物是代谢谱的一部分，可能为法布里病的病理生理学提供深入了解。
