Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis
Abstract Background Metabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1625-1 |
| _version_ | 1828201480490844160 |
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| author | Abdellah Tebani Lenaig Abily-Donval Isabelle Schmitz-Afonso Bénédicte Héron Monique Piraud Jérôme Ausseil Farid Zerimech Bruno Gonzalez Stéphane Marret Carlos Afonso Soumeya Bekri |
| author_facet | Abdellah Tebani Lenaig Abily-Donval Isabelle Schmitz-Afonso Bénédicte Héron Monique Piraud Jérôme Ausseil Farid Zerimech Bruno Gonzalez Stéphane Marret Carlos Afonso Soumeya Bekri |
| author_sort | Abdellah Tebani |
| collection | DOAJ |
| description | Abstract Background Metabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mucopolysaccharidosis type III (MPS III). A thorough and holistic understanding of metabolic remodeling in MPS III may allow the development, improvement and personalization of patient care. Methods We applied both targeted and untargeted metabolomics to urine samples obtained from a French cohort of 49 patients, consisting of 13 MPS IIIA, 16 MPS IIIB, 13 MPS IIIC, and 7 MPS IIID, along with 66 controls. The analytical strategy is based on ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Twenty-four amino acids have been assessed using tandem mass spectrometry combined with liquid chromatography. Multivariate data modeling has been used for discriminant metabolite selection. Pathway analysis has been performed to retrieve metabolic pathways impairments. Results Data analysis revealed distinct biochemical profiles. These metabolic patterns, particularly those related to the amino acid metabolisms, allowed the different studied groups to be distinguished. Pathway analysis unveiled major amino acid pathways impairments in MPS III mainly arginine–proline metabolism and urea cycle metabolism. Conclusion This represents one of the first metabolomics-based investigations of MPS III. These results may shed light on MPS III pathophysiology and could help to set more targeted studies to infer the biomarkers of the affected pathways, which is crucial for rare conditions such as MPS III. |
| first_indexed | 2024-04-12T11:31:51Z |
| format | Article |
| id | doaj.art-2a82a7d9a17a4d6fa0fa6281709f1a3a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T11:31:51Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2a82a7d9a17a4d6fa0fa6281709f1a3a2022-12-22T03:34:59ZengBMCJournal of Translational Medicine1479-58762018-09-0116111410.1186/s12967-018-1625-1Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysisAbdellah Tebani0Lenaig Abily-Donval1Isabelle Schmitz-Afonso2Bénédicte Héron3Monique Piraud4Jérôme Ausseil5Farid Zerimech6Bruno Gonzalez7Stéphane Marret8Carlos Afonso9Soumeya Bekri10Department of Metabolic Biochemistry, Rouen University HospitalNormandie Univ, UNIROUEN, CHU Rouen, INSERM U1245Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRADepartment of Pediatric Neurology, Reference Center of Lysosomal Diseases, Trousseau Hospital, APHP and Sorbonne UniversitéService de Biochimie et Biologie Moléculaire Grand Est, Unité des Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et de Pathologie EstINSERM U1088, Laboratoire de Biochimie Métabolique, Centre de Biologie Humaine, CHU SudLaboratoire de Biochimie et Biologie Moléculaire, Université de Lille et Pôle de Biologie Pathologie Génétique du CHRU de LilleNormandie Univ, UNIROUEN, CHU Rouen, INSERM U1245Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRADepartment of Metabolic Biochemistry, Rouen University HospitalAbstract Background Metabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mucopolysaccharidosis type III (MPS III). A thorough and holistic understanding of metabolic remodeling in MPS III may allow the development, improvement and personalization of patient care. Methods We applied both targeted and untargeted metabolomics to urine samples obtained from a French cohort of 49 patients, consisting of 13 MPS IIIA, 16 MPS IIIB, 13 MPS IIIC, and 7 MPS IIID, along with 66 controls. The analytical strategy is based on ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Twenty-four amino acids have been assessed using tandem mass spectrometry combined with liquid chromatography. Multivariate data modeling has been used for discriminant metabolite selection. Pathway analysis has been performed to retrieve metabolic pathways impairments. Results Data analysis revealed distinct biochemical profiles. These metabolic patterns, particularly those related to the amino acid metabolisms, allowed the different studied groups to be distinguished. Pathway analysis unveiled major amino acid pathways impairments in MPS III mainly arginine–proline metabolism and urea cycle metabolism. Conclusion This represents one of the first metabolomics-based investigations of MPS III. These results may shed light on MPS III pathophysiology and could help to set more targeted studies to infer the biomarkers of the affected pathways, which is crucial for rare conditions such as MPS III.http://link.springer.com/article/10.1186/s12967-018-1625-1MetabolomicsInborn errors of metabolismMucopolysaccharidosis type IIILysosomal storage diseasesMass spectrometryIon mobility |
| spellingShingle | Abdellah Tebani Lenaig Abily-Donval Isabelle Schmitz-Afonso Bénédicte Héron Monique Piraud Jérôme Ausseil Farid Zerimech Bruno Gonzalez Stéphane Marret Carlos Afonso Soumeya Bekri Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis Journal of Translational Medicine Metabolomics Inborn errors of metabolism Mucopolysaccharidosis type III Lysosomal storage diseases Mass spectrometry Ion mobility |
| title | Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis |
| title_full | Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis |
| title_fullStr | Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis |
| title_full_unstemmed | Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis |
| title_short | Unveiling metabolic remodeling in mucopolysaccharidosis type III through integrative metabolomics and pathway analysis |
| title_sort | unveiling metabolic remodeling in mucopolysaccharidosis type iii through integrative metabolomics and pathway analysis |
| topic | Metabolomics Inborn errors of metabolism Mucopolysaccharidosis type III Lysosomal storage diseases Mass spectrometry Ion mobility |
| url | http://link.springer.com/article/10.1186/s12967-018-1625-1 |
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