9 genetic defects in bile acid biosynthesis pathway which cause various degree of liver injury in patients were identified and described. HSD3B7 deficiency is the most commonly occurring defect and can lead to morbidity or mortality in patients if not diagnosed and treated. By applying untargeted metabolomics platform to analyze normal and patient urine samples, we were able to confirm these biomarkers, namely Δ5-cholen-24-oic acid derivatives in patient urine. These signature compounds were then obtained with sophisticated multistep synthesis and used to set up a sensitive, robust analytical assay enabling accurate quantification. Data from two systems were highly correlated and the combined approach proved to be very effective in facilitating diagnosis of the deficiency, monitor and assessment of therapeutic response.
Application of Untargeted and Targeted Metabolomics to the Study of Liver Disease Caused by a Deficiency in HSD3B7-diagnosis and Response to Therapy
GIOIELLO, ANTIMO;B. Cerra;PELLICCIARI, Roberto;
2014
Abstract
9 genetic defects in bile acid biosynthesis pathway which cause various degree of liver injury in patients were identified and described. HSD3B7 deficiency is the most commonly occurring defect and can lead to morbidity or mortality in patients if not diagnosed and treated. By applying untargeted metabolomics platform to analyze normal and patient urine samples, we were able to confirm these biomarkers, namely Δ5-cholen-24-oic acid derivatives in patient urine. These signature compounds were then obtained with sophisticated multistep synthesis and used to set up a sensitive, robust analytical assay enabling accurate quantification. Data from two systems were highly correlated and the combined approach proved to be very effective in facilitating diagnosis of the deficiency, monitor and assessment of therapeutic response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
