NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls
Abstract Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive, neurodegenerative lysosomal storage disorder, which presents with a range of clinical phenotypes and hence diagnosis remains a challenge. In view of these difficulties, the search for a novel, NPC1-specific biomarker (or set...
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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06264-2 |
| _version_ | 1818754243715137536 |
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| author | Fay Probert Victor Ruiz-Rodado Danielle te Vruchte Elena-Raluca Nicoli Tim D. W. Claridge Christopher A. Wassif Nicole Farhat Forbes D. Porter Frances M. Platt Martin Grootveld |
| author_facet | Fay Probert Victor Ruiz-Rodado Danielle te Vruchte Elena-Raluca Nicoli Tim D. W. Claridge Christopher A. Wassif Nicole Farhat Forbes D. Porter Frances M. Platt Martin Grootveld |
| author_sort | Fay Probert |
| collection | DOAJ |
| description | Abstract Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive, neurodegenerative lysosomal storage disorder, which presents with a range of clinical phenotypes and hence diagnosis remains a challenge. In view of these difficulties, the search for a novel, NPC1-specific biomarker (or set of biomarkers) is a topic of much interest. Here we employed high-resolution 1H nuclear magnetic resonance spectroscopy coupled with advanced multivariate analysis techniques in order to explore and seek differences between blood plasma samples acquired from NPC1 (untreated and miglustat treated), heterozygote, and healthy control subjects. Using this approach, we were able to identify NPC1 disease with 91% accuracy confirming that there are significant differences in the NMR plasma metabolic profiles of NPC1 patients when compared to healthy controls. The discrimination between NPC1 (both miglustat treated and untreated) and healthy controls was dominated by lipoprotein triacylglycerol 1H NMR resonances and isoleucine. Heterozygote plasma samples displayed also increases in the intensities of selected lipoprotein triacylglycerol 1H NMR signals over those of healthy controls. The metabolites identified could represent useful biomarkers in the future and provide valuable insight in to the underlying pathology of NPC1 disease. |
| first_indexed | 2024-12-18T05:20:10Z |
| format | Article |
| id | doaj.art-486e2509b932488d83bb2463ee51ff9c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:20:10Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-486e2509b932488d83bb2463ee51ff9c2022-12-21T21:19:40ZengNature PortfolioScientific Reports2045-23222017-07-017111210.1038/s41598-017-06264-2NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controlsFay Probert0Victor Ruiz-Rodado1Danielle te Vruchte2Elena-Raluca Nicoli3Tim D. W. Claridge4Christopher A. Wassif5Nicole Farhat6Forbes D. Porter7Frances M. Platt8Martin Grootveld9Department of Pharmacology, De Montfort UniversityDepartment of Pharmacology, De Montfort UniversityDepartment of Pharmacology, University of OxfordDepartment of Pharmacology, University of OxfordDepartment of Chemistry, University of OxfordDepartment of Pharmacology, University of OxfordSection of Molecular Dysmorphology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Department of Health and Human ServicesSection of Molecular Dysmorphology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Department of Health and Human ServicesDepartment of Pharmacology, University of OxfordDepartment of Pharmacology, De Montfort UniversityAbstract Niemann-Pick type C1 (NPC1) disease is a rare autosomal recessive, neurodegenerative lysosomal storage disorder, which presents with a range of clinical phenotypes and hence diagnosis remains a challenge. In view of these difficulties, the search for a novel, NPC1-specific biomarker (or set of biomarkers) is a topic of much interest. Here we employed high-resolution 1H nuclear magnetic resonance spectroscopy coupled with advanced multivariate analysis techniques in order to explore and seek differences between blood plasma samples acquired from NPC1 (untreated and miglustat treated), heterozygote, and healthy control subjects. Using this approach, we were able to identify NPC1 disease with 91% accuracy confirming that there are significant differences in the NMR plasma metabolic profiles of NPC1 patients when compared to healthy controls. The discrimination between NPC1 (both miglustat treated and untreated) and healthy controls was dominated by lipoprotein triacylglycerol 1H NMR resonances and isoleucine. Heterozygote plasma samples displayed also increases in the intensities of selected lipoprotein triacylglycerol 1H NMR signals over those of healthy controls. The metabolites identified could represent useful biomarkers in the future and provide valuable insight in to the underlying pathology of NPC1 disease.https://doi.org/10.1038/s41598-017-06264-2 |
| spellingShingle | Fay Probert Victor Ruiz-Rodado Danielle te Vruchte Elena-Raluca Nicoli Tim D. W. Claridge Christopher A. Wassif Nicole Farhat Forbes D. Porter Frances M. Platt Martin Grootveld NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls Scientific Reports |
| title | NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls |
| title_full | NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls |
| title_fullStr | NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls |
| title_full_unstemmed | NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls |
| title_short | NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls |
| title_sort | nmr analysis reveals significant differences in the plasma metabolic profiles of niemann pick c1 patients heterozygous carriers and healthy controls |
| url | https://doi.org/10.1038/s41598-017-06264-2 |
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