Lipidomics and metabolomics for rare disease diagnosis

Lead Research Organisation: Swansea University
Department Name: Institute of Life Science Medical School


One of the top priorities set out by the UK Rare Diseases Framework is to help patients get a final diagnosis faster. There are an estimated 6,000-8,000 rare diseases, including over 1,000 inborn metabolic disorders. The majority of rare disease patients experience the diagnostic odyssey, including diagnosis delay, misdiagnosis, or no correct diagnosis. Harnessing the power of gene technology for patient care has made a significant advance, but gene sequencing is mostly limited to diagnosing patients with known mutations. To further transform rare disease diagnosis, biochemical methods including metabolomics, and gene sequencing technology need to be developed together and integrated. Clinicians want more global and efficient assays which can identify what is the cause of the medical problem and can rule out other conditions in an initial assessment with a fast turnaround time.

UK academic laboratories specialising in mass spectrometry have world-leading expertise in global metabolite analysis, known as metabolomics. Currently this technology is only used in ad hoc research collaborations, and the majority of patients do not directly benefit from such recent technology developments.

To address the challenges in rare disease diagnosis, by bringing together, bioanalysts including experts in metabolomics, clinical scientists, clinicians, geneticists, biostatisticians and patient groups, from across the four nations of the UK, our node aims to establish new routes for clinical access to multiplexed lipidomic/metabolomic assays targeted at rare diseases, enabling earlier diagnosis, intervention and improved clinical outcomes.

Technical Summary

Mass spectrometry (MS) offers high specificity of metabolite identification and quantification and is routinely used for newborn screening and by NHS metabolic laboratories. Recent advances in MS based metabolomics and lipidomics allow the quantitative profiling of a large number (>1,000) of metabolites in a given sample. MS is a powerful tool to reveal biochemical abnormalities and to facilitate rare disease diagnosis in combination with genomics and other biochemical assays. This project will bring MS expertise from the UK lipidomic/metabolomic community into the domain of rare disease diagnosis. It will translate the latest lipidomic/metabolomic methods from a research settings to the clinical laboratory.

Specifically, we will:

(1) Translate enhanced screening assays for rare lipid and metabolic disorders from the research laboratory to the NHS metabolic laboratory.
(2) Integrate metabolomics with genomics for diagnosis of Syndromes Without A Name.

With further technological development, i.e., faster sample turn-around and lower cost, we aim to incorporate more lipidomic/metabolomic technology into the diagnostic pathways as well as considering its future application to newborn screening programmes, allowing asymptomatic patients to be identified and diagnosed. The node will be open to new members who bring in different "omic" expertise including bioinformaticians and economists, also to new clinical centres with the challenge of diagnosing patients with rare metabolic disorders.


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