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Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics

Department of Metabolic Biochemistry, Rouen University Hospital, 76000 Rouen, France
Normandie University, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, France
Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA, 76000 Rouen, France
Department of Neonatal Pediatrics, Intensive Care and Neuropediatrics, Rouen University Hospital, 76031 Rouen, France
Service de Biochimie et Biologie Moléculaire Grand Est, Unité des Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 69002 Lyon, France
INSERM U1088, Laboratoire de Biochimie Métabolique, Centre de Biologie Humaine, CHU Sud, 80054 Amiens CEDEX, France
Laboratoire de Biochimie et Biologie Moléculaire, Université de Lille et Pôle de Biologie Pathologie Génétique du CHRU de Lille, 59000 Lille, France
Department of Pharmacology, Rouen University Hospital, 76000 Rouen, France
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 446;
Received: 17 December 2018 / Revised: 17 January 2019 / Accepted: 18 January 2019 / Published: 21 January 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Metabolic phenotyping is poised as a powerful and promising tool for biomarker discovery in inherited metabolic diseases. However, few studies applied this approach to mcopolysaccharidoses (MPS). Thus, this innovative functional approach may unveil comprehensive impairments in MPS biology. This study explores mcopolysaccharidosis VI (MPS VI) or Maroteaux–Lamy syndrome (OMIM #253200) which is an autosomal recessive lysosomal storage disease caused by the deficiency of arylsulfatase B enzyme. Urine samples were collected from 16 MPS VI patients and 66 healthy control individuals. Untargeted metabolomics analysis was applied using ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Furthermore, dermatan sulfate, amino acids, carnitine, and acylcarnitine profiles were quantified using liquid chromatography coupled to tandem mass spectrometry. Univariate analysis and multivariate data modeling were used for integrative analysis and discriminant metabolites selection. Pathway analysis was done to unveil impaired metabolism. The study revealed significant differential biochemical patterns using multivariate data modeling. Pathway analysis revealed that several major amino acid pathways were dysregulated in MPS VI. Integrative analysis of targeted and untargeted metabolomics data with in silico results yielded arginine-proline, histidine, and glutathione metabolism being the most affected. This study is one of the first metabolic phenotyping studies of MPS VI. The findings might shed light on molecular understanding of MPS pathophysiology to develop further MPS studies to enhance diagnosis and treatments of this rare condition. View Full-Text
Keywords: metabolomics; inherited metabolic diseases; lysosomal storage diseases; mucopolysaccharidosis type VI; Maroteaux–Lamy syndrome; mass spectrometry metabolomics; inherited metabolic diseases; lysosomal storage diseases; mucopolysaccharidosis type VI; Maroteaux–Lamy syndrome; mass spectrometry
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Tebani, A.; Abily-Donval, L.; Schmitz-Afonso, I.; Piraud, M.; Ausseil, J.; Zerimech, F.; Pilon, C.; Pereira, T.; Marret, S.; Afonso, C.; Bekri, S. Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics. Int. J. Mol. Sci. 2019, 20, 446.

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