Global metabolomics analysis of serum from patients with Niemann–Pick disease type C

抄録

Niemann–Pick disease type C (NPC) is an autosomal recessive disorder with a wide clinical spectrum. NPC is caused by a lack of cholesterol transport proteins. In recent years, various lipid-derived biomarkers for NPC have been identified, suggesting extensive abnormal metabolism of various lipids. Global metabolomics is a technique that enables qualitative and semi-quantitative analysis based on accurate mass spectrometry combined with liquid chromatography. It is also useful for identifying biomarkers. In this study, a global metabolomics approach was applied to serum from patients with NPC to clarify lipid metabolism abnormalities. Serum samples were analyzed by liquid chromatographic separation with gradient elution and high-resolution mass spectrometry. After post-processing, all datasets were subjected to multivariate analysis. Principal component analysis showed overlapping of sample groups between healthy subjects and NPC patients. Orthogonal partial least square-discriminant analysis detected characteristic peaks corresponding to metabolites such as N-palmitoyl-O-phosphocholine-serine and sphingosylphosphorylcholine, which have previously been reported as biomarkers of NPC. Novel changes in levels of metabolites such as lysophosphatidylinositol were also observed in NPC, and peaks indicating the existence of a novel metabolic pathway, involving metabolites such as N-acylserine, were also detected. These results indicate that global metabolomics is useful for comprehensive analysis of metabolic changes in NPC pathology.