Untargeted LC-HRMS metabolomics reveals candidate biomarkers for mucopolysaccharidoses.

Abstract

BACKGROUND:

Mucopolysaccharidoses (MPSs) are inherited genetic diseases caused by an absence or deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Undiagnosed patients, or those without adequate treatment in early life, can be severely and irreversibly affected by the disease. In this study, we applied liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based untargeted metabolomics to identify potential biomarkers for MPS disorders to better understand how MPS may affect the metabolome of patients.

METHODS:

Urine samples from 37 MPS patients (types I, II, III, IV, and VI; untreated and treated with enzyme replacement therapy (ERT)) and 38 controls were analyzed by LC-HRMS. Data were processed by an untargeted metabolomics workflow and submitted to multivariate statistical analyses to reveal significant differences between the MPS and control groups.

RESULTS:

A total of 12 increased metabolites common to all MPS types were identified. Dipeptides, amino acids and derivatives were increased in the MPS group compared to controls. N-acetylgalactosamines 4- or 6-sulfate, important constituents of GAGs, were also elevated in MPS patients, most prominently in those with MPS VI. Notably, treated patients exhibited lower levels of the aforementioned acylaminosugars than untreated patients in all MPS types.

CONCLUSIONS:

Untargeted metabolomics has enabled the detection of metabolites that could improve our understanding of MPS physiopathology. These potential biomarkers can be utilized in screening methods to support diagnosis and ERT monitoring.

• Authors: Clarisse L Torres, Fernanda B Scalco, Maria Lúcia C de Oliveira, Roy W A Peake, Rafael Garrett
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 541 Pg. 117250 (Feb 15 2023) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 36764508 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Heparitin Sulfate
• Dermatan Sulfate
• Glycosaminoglycans
• Biomarkers

Topics

• Humans
• Heparitin Sulfate (urine)
• Dermatan Sulfate (urine)
• Tandem Mass Spectrometry (methods)
• Mucopolysaccharidoses (diagnosis)
• Glycosaminoglycans (urine)
• Chromatography, Liquid (methods)
• Metabolomics (methods)
• Biomarkers (urine)