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Urinary Metabolic Fingerprint of Acute Intermittent Porphyria Analyzed by 1H NMR Spectroscopy

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journal contribution
posted on 18.02.2014, 00:00 by Mickael Carichon, Nicolas Pallet, Caroline Schmitt, Thibaud Lefebvre, Laurent Gouya, Neila Talbi, Jean Charles Deybach, Philippe Beaune, Paul Vasos, Hervé Puy, Gildas Bertho
1H NMR is a nonbiased technique for the quantification of small molecules that could result in the identification and characterization of potential biomarkers with prognostic value and contribute to better understand pathophysiology of diseases. In this study, we used 1H NMR spectroscopy to analyze the urinary metabolome of patients with acute intermittent porphyria (AIP), an inherited metabolic disorder of heme biosynthesis in which an accumulation of the heme precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG) promotes sudden neurovisceral attacks, which can be life-threatening. Our objectives were (1) to demonstrate the usefulness of 1H NMR to identify and quantify ALA and PBG in urines from AIP patients and (2) to identify metabolites that would predict the response to AIP crisis treatment and reflect differential metabolic reprogramming. Our results indicate that 1H NMR can help to diagnose AIP attacks based on the identification of ALA and PBG. We also show that glycin concentration increases in urines from patients with frequent recurrences at the end of the treatment, after an initial decrease, whereas PBG concentration remains low. Although the reasons for this altered are elusive, these findings indicate that a glycin metabolic reprogramming occurs in AIPr patients and is associated with recurrence. Our results validate the proof of concept of the usefulness of 1H NMR spectroscopy in clinical chemistry for the diagnosis of acute attack of AIP and identify urinary glycin as a potential marker of recurrence of AIP acute attacks.