Combined targeted and untargeted high-resolution mass spectrometry analyses to investigate metabolic alterations in pompe disease.

Autor: de Moraes MBM; Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Av. Horácio Macedo 1281, Rio de Janeiro, RJ, 21941-598, Brazil., de Souza HMR; Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Av. Horácio Macedo 1281, Rio de Janeiro, RJ, 21941-598, Brazil.; Institute of Chemistry, Fluminense Federal University, Niterói, RJ, Brazil., de Oliveira MLC; Inborn Error of Metabolism Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Peake RWA; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Scalco FB; Inborn Error of Metabolism Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Garrett R; Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, Av. Horácio Macedo 1281, Rio de Janeiro, RJ, 21941-598, Brazil. rafael_garrett@iq.ufrj.br.; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. rafael_garrett@iq.ufrj.br.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2023 Mar 29; Vol. 19 (4), pp. 29. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1007/s11306-023-01989-w
Abstrakt: Introduction: Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of α-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe.
Objective: The purpose of the present study was to develop a simple methodology using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for targeted quantitative analysis of Glc 4 combined with untargeted metabolic profiling in a single analytical run to search for complementary biomarkers in Pompe disease.
Methods: We collected 21 urine specimens from 13 Pompe disease patients and compared their metabolic signatures with 21 control specimens.
Results: Multivariate statistical analyses on the untargeted profiling data revealed Glc 4 , creatine, sorbitol/mannitol, L-phenylalanine, N-acetyl-4-aminobutanal, N-acetyl-L-aspartic acid, and 2-aminobenzoic acid as significantly altered in Pompe disease. This panel of metabolites increased sample class prediction (Pompe disease versus control) compared with a single biomarker.
Conclusion: This study has demonstrated the potential of combined acquisition methods in LC-HRMS for Pompe disease investigation, allowing for routine determination of an established biomarker and discovery of complementary candidate biomarkers that may increase diagnostic accuracy, or improve the risk stratification of patients with disparate clinical phenotypes.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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