Introduction: Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease.
Objectives: In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses.
Methods: Urine 1H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained.
Results: Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients.
Conclusion: These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.
Keywords: 1H NMR; Biomarkers; Porphyrias; Subgroup discovery.