1H NMR-based metabolomics: Chemometric methods for the diagnosis of inborn errors of metabolism

Background: 1H-NMR spectroscopy has successfully been applied to the field of inborn errors of metabolism (IEM). However, body fluid NMR spectra lead to a wealth of data and it can be a daunting task to find the relevant information. In this study, chemometric methods were used to analyze urine NMR data. Objectives: To investigate the use of chemometric methods in NMR-based urine analysis to diagnose patients with IEM. Alkaptonuria (ALK) and methylmalonic aciduria (MMA) will be used as examples. Material/Methods: 1H-NMR spectroscopy was performed on urine from 58 healthy volunteers, 5 patients with ALK and 6 patients with MMA. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied in order to establish models for discrimination between diseased and normal urine samples. Results: Discrimination of ALK and MMA urine from healthy urine was achieved by the different models produced by PCA and PLS-DA. Comparing the two methods, PLS-DA was found to give the best discrimination between the 3 groups. The resonances of the diagnostic metabolites for both diseases could easily be found with both techniques. Conclusion/Discussion: Chemometrics analyses can assist the interpretation of complex body fluid NMR data and may be useful in the rapid screening of patients with IEM.