New Developments in the NMR-Linked Metabolomics Analysis of Lysosomal Storage Disorders
Lysosomal storage disorders (LSDs) are predominantly rare, autosomal recessive, orphan diseases that impact the storage of specific molecules within the lysosome. This work explores current metabolomics research on LSDs with a specific focus on Niemann Pick Disease Type C, Gaucher’s Disease and Gangliosidoses. Moreover, metabolomic techniques are explored with a history and theory outlined for nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometric analytical strategies. Statistical analyses, particularly multivariate approaches, and machine learning applied to the analysis of these metabolomic datasets are also discussed. Human urinary and plasma metabolomics investigations were then performed using the 1H NMR technique on samples provided from Gaucher’s Disease and GM1 Type II patients with corresponding controls. Furthermore, using a feline model, a 1H NMR urinary investigation was performed to investigate the impact of Niemann Pick Disease Type C on the metabolome, and also to evaluate metabolic changes in felines treated with 2-hydroxypropyl-β-cyclodextrin. Statistical evaluations were performed for all three conditions, and the significance of these are highlighted, with some key potential biomarkers identified. The advantages of using a 1H NMR approach are summarised, in addition to the challenges of performing complex metabolomics analysis of LSDs, with particular considerations of the limited sample sizes of these available for such studies.
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