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.

Details

Title
NMR analysis reveals significant differences in the plasma metabolic profiles of Niemann Pick C1 patients, heterozygous carriers, and healthy controls
Author
Probert, Fay 1 ; Ruiz-Rodado, Victor 2 ; Danielle te Vruchte 3 ; Elena-Raluca Nicoli 3 ; Claridge, Tim D W 4   VIAFID ORCID Logo  ; Wassif, Christopher A 5 ; Farhat, Nicole 6 ; Porter, Forbes D 6 ; Platt, Frances M 3 ; Grootveld, Martin 2 

 Department of Pharmacology, De Montfort University, Leicester, UK; Department of Pharmacology, University of Oxford, Oxford, UK 
 Department of Pharmacology, De Montfort University, Leicester, UK 
 Department of Pharmacology, University of Oxford, Oxford, UK 
 Department of Chemistry, University of Oxford, Oxford, UK 
 Department of Pharmacology, University of Oxford, Oxford, UK; Section of Molecular Dysmorphology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Department of Health and Human Services, Bethesda, MD, USA 
 Section of Molecular Dysmorphology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Department of Health and Human Services, Bethesda, MD, USA 
Pages
1-12
Publication year
2017
Publication date
Jul 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1956152260
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.