Mitochondrial diseases can be difficult to recognise clinically making them difficult to diagnose, even with extensive testing over many years. It would be a significant advance to develop and implement biomarker tests that improve frontline diagnostic indication of mitochondrial diseases. The aim of this project was to refine a metabolic phenotyping approach already developed by Dr Davis by seeing if disease cohorts that represent components of mitochondrial disease appear similar by this approach.
Various clinical cohorts that closely resemble components of mitochondrial disease (e.g. diabetes, macular degeneration, neuromuscular conditions) were collected from departments within Royal North Shore Hospital and Westmead Hospital. Serum and urine samples were collected for analysis of all small chemical metabolites using an untargeted metabolic phenotyping approach called Nuclear Magnetic Resonance Spectroscopy. A targeted metabolic phenotyping approach (e.g. Koay, FASEB J, 33(7): 8033) was also sought for comparison with the untargeted approach and with implementation of a clinical test in mind.
A multivariate metabolic diagnostic model of mitochondrial disease has been refined from this study. Application of the metabolites of interest and further refinement onto the targeted metabolomic platform (Liquid Chromatography coupled to Mass Spectrometry) will allow eventual translation and application of this test for clinical diagnostic use by Pathology labs.
As a direct outcome of the work carried out, a number of other projects have been developed that will utilise the expertise gained and the methodology.