2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Designing an Untargeted Metabolomics Assay to Detect Biomarkers for Inborn Errors of Metabolism in the Clinical Laboratory

Pdf Summary

This document discusses the development of an untargeted metabolomics assay for the detection of biomarkers related to inborn errors of metabolism (IEMs) in the clinical laboratory. IEMs are inherited disorders that affect metabolism and can be diagnosed through the evaluation of metabolites. The untargeted approach allows for the analysis of multiple metabolites simultaneously, potentially uncovering new biomarkers and aiding in the characterization of novel conditions.<br /><br />The study found that 88% of the reference standards were detected by the assay. The hydrophilic interaction liquid chromatography (HILIC) column detected 71% of the standards, while the reverse phase (RP) column detected 33%. Both columns resolved 17% of the standards. In the presence of plasma, 4% of the standards were suppressed to levels below the limit of detection.<br /><br />Internal standard retention time stability was assessed, and the assay demonstrated good stability with low variation between batches. The sample preparation involved analyzing a mixture of 165 reference standards from various compound classes common to IEMs. Chromatographic resolution for each standard was determined by comparison to a reference spectral database.<br /><br />The assay utilized a dual-liquid chromatography quadrupole time-of-flight mass spectrometry method. The X500B QTOF system operated in data-independent acquisition mode. Future directions for the research include biomarker discovery in patient cohorts and the characterization of different sample types.<br /><br />In conclusion, the untargeted metabolomics assay demonstrated the ability to detect known biomarkers for IEMs. It has the potential to streamline the diagnosis of IEMs and improve patient outcomes by leveraging the metabolome for biomarker discovery and understanding IEM mechanisms for novel treatment strategies.

Asset Subtitle

Presenting Author - Rachel Wurth, MS; Co-Author - Coleman Turgeon, MS; Co-Author - Zinandré Stander, PhD; Co-Author - Dimitar K. Gavrilov, MD, PhD; Co-Author - Patricia L. Hall, PhD; Co-Author - Dietrich Matern, MD, PhD, FACMG; Co-Author - Matthew Schultz, PhD; Co-Author - Silvia Tortorelli, MD,PhD; Co-Author - Devin Oglesbee, PhD;

Meta Tag

Metabolic Disorder

Lysosomal Diseases

Differentiation

Biochemical genetics

Co-Author Devin Oglesbee, PhD

Co-Author Silvia Tortorelli, MD,PhD

Co-Author Matthew Schultz, PhD

Co-Author Dietrich Matern, MD, PhD, FACMG

Co-Author Patricia L. Hall, PhD

Co-Author Dimitar K. Gavrilov, MD, PhD

Co-Author Zinandré Stander, PhD

Co-Author Coleman Turgeon, MS

Presenting Author Rachel Wurth, MS

Keywords

untargeted metabolomics assay

biomarkers

inborn errors of metabolism

clinical laboratory

metabolites

diagnosis

hydrophilic interaction liquid chromatography

reverse phase column

plasma

internal standard retention time stability