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Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics
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 stud...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359186/ https://www.ncbi.nlm.nih.gov/pubmed/30669586 http://dx.doi.org/10.3390/ijms20020446 |
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author | Tebani, Abdellah Abily-Donval, Lenaig Schmitz-Afonso, Isabelle Piraud, Monique Ausseil, Jérôme Zerimech, Farid Pilon, Carine Pereira, Tony Marret, Stéphane Afonso, Carlos Bekri, Soumeya |
author_facet | Tebani, Abdellah Abily-Donval, Lenaig Schmitz-Afonso, Isabelle Piraud, Monique Ausseil, Jérôme Zerimech, Farid Pilon, Carine Pereira, Tony Marret, Stéphane Afonso, Carlos Bekri, Soumeya |
author_sort | Tebani, Abdellah |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6359186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63591862019-02-06 Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics Tebani, Abdellah Abily-Donval, Lenaig Schmitz-Afonso, Isabelle Piraud, Monique Ausseil, Jérôme Zerimech, Farid Pilon, Carine Pereira, Tony Marret, Stéphane Afonso, Carlos Bekri, Soumeya Int J Mol Sci Article 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. MDPI 2019-01-21 /pmc/articles/PMC6359186/ /pubmed/30669586 http://dx.doi.org/10.3390/ijms20020446 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tebani, Abdellah Abily-Donval, Lenaig Schmitz-Afonso, Isabelle Piraud, Monique Ausseil, Jérôme Zerimech, Farid Pilon, Carine Pereira, Tony Marret, Stéphane Afonso, Carlos Bekri, Soumeya Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title | Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title_full | Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title_fullStr | Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title_full_unstemmed | Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title_short | Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics |
title_sort | analysis of mucopolysaccharidosis type vi through integrative functional metabolomics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359186/ https://www.ncbi.nlm.nih.gov/pubmed/30669586 http://dx.doi.org/10.3390/ijms20020446 |
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