Christiane Auray-Blais
Université de Sherbrooke, Canada
Title: Mass Spectrometry Approaches for Translational Research: From Biomarker Discovery to Clinical Applications
Biography
Biography: Christiane Auray-Blais
Abstract
In order to increase the number of treatable disorders screened by the Mass Urinary Screening Program in the Province of Quebec, we developed and validated a tandem mass spectrometry multiplex method for creatine synthesis and transport disorders, Triple H syndrome and ornithine transcarbamylase deficiency. We targeted specific-related biomarkers such as creatine, guanidineacetate, uracil, orotic acid and creatinine using urine collected on filter paper. This method showed good linearity with a mean coefficient of regression at 0.9985 for all metabolites, as well as precision and accuracy for the intraday and interday assays at 15%. All abnormal patients were well discriminated from controls. We have shown that this methodology is feasible for mass or high-risk screening with high sensitivity and reproducibility. Regarding lysosomal storage disorders, we have performed a time of flight mass spectrometry metabolomic study for biomarker discovery for Fabry disease, a multisystemic, X-linked complex disorder. We detected novel analogues of a glycosphingolipid, globotriaosylsphingosine (lyso-Gb3), which were found to be increased in Fabry patients presenting the cardiac variant mutation of the disease. Robust tandem mass spectrometry methods were devised and validated for both urine and plasma. We have also devised a UPLC-MS/MS method for methylated and non-methylated forms of globoriaosylceramide (Gb3), another biomarker detected in Fabry disease patients. These latter methods allowed the quantification of biomarkers in biological fluids of affected Fabry patients and controls, and are aimed at the evaluation of correlations to determine disease-severity and progression.