Untargeted metabolomics in IMD diagnosis, a feasibility study
Research type
Research Study
Full title
Untargeted metabolomics as a diagnostic test for inherited metabolic disease, a feasibility study to translate a research tool into an NHS clinical laboratory.
IRAS ID
312010
Contact name
Greg Toulson
Contact email
Sponsor organisation
Birmingham Children's Hospital
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Whilst individually rare, the cumulative incidence of inherited metabolic disease (IMD) is common. Conditions range in severity from fatal to mild; many are manageable with diet and/or medication. Diagnosis often requires multiple biochemical tests; for rarer conditions, testing may not be readily available. Metabolomics is a new field that measures thousands of components in a single blood sample, providing a broad overview of bodily metabolism and any apparent defects. This project aims to assess the potential of translating this technique from disease research to routine hospital testing, reducing time to diagnosis and identifying cases that current approaches struggle to identify.
This project’s primary aim is a proof-of-concept for the clinical utility of using untargeted metabolomics as an IMD screen within the UK. To this end a collaboration between an NHS clinical laboratory and The Phenome Centre Birmingham (PCB) is proposed, leveraging the expertise and equipment of academic leaders to translate new technologies into clinical practice. Improving on previously attempted studies, our approach would utilise a Hybrid Quadrupole-Orbitrap mass-spectrometry platform paired with HILIC chromatography, improving resolution and IMD relevant metabolite identification.
Over an 18-month period, 75 plasma samples from a range of IMD patients who received a subsequent diagnosis would be collected in addition to 30 age-matched controls. Samples used would be remnant material, the material left over following the completion of routine biochemical investigations. After consent agreed with participating patients and their families, samples would anonymised and transfered to PCB and analysed using a standardised metabolomics workflow and a selection of different post-hoc analyses applied before the outputs are assessed in order to make a blinded diagnosis. This study should provide the foundation for a future, more comprehensive programme aimed at clinical validation.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
22/SC/0101
Date of REC Opinion
23 May 2022
REC opinion
Further Information Favourable Opinion