A Metabolomic Study To Identify New Globotriaosylceramide-Related Biomarkers in the Plasma of Fabry Disease Patients
2013
Manwaring, Victoria | Boutin, Michel | Auray-Blais, Christiane
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.
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