Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tebani, Abdellah, Abily-Donval, Lenaig, Schmitz-Afonso, Isabelle, Piraud, Monique, Ausseil, Jérôme, Zerimech, Farid, Pilon, Carine, Pereira, Tony, Marret, Stéphane, Afonso, Carlos, Bekri, Soumeya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783392173869236224
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
work_keys_str_mv AT tebaniabdellah analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT abilydonvallenaig analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT schmitzafonsoisabelle analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT piraudmonique analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT ausseiljerome analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT zerimechfarid analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT piloncarine analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT pereiratony analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT marretstephane analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT afonsocarlos analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics
AT bekrisoumeya analysisofmucopolysaccharidosistypevithroughintegrativefunctionalmetabolomics