LC-MS/MS for Endogenous Metabolites for Developing Diagnostic Biomarkers of Niemann-Pick Diseases

Abstract

To analyze of endogenous metabolites in diseases is useful for discovering diagnostic biomarkers and elucidating molecular mechanisms of pathogenesis. Niemann-Pick disease type C (NPC) is a autosomal recessive disease with diverse onset times and clinical symptoms, and there were some problems with conventional diagnostic methods. Therefore, we have worked on the developing the biomarkers for NPC using LC-MS/MS analysis. First, we focused on conjugated cholesterol metabolites excreted in large amounts in the urine of NPC patients, and our analysis using LC-MS/MS revealed that several metabolites are useful as diagnostic markers. Next, we aimed to identify the unknown molecule lysosphingomyelin-509, which has been used for screening in Europe and America, and successfully determined its structure using microchemical approaches. In addition, we also developed a novel diagnostic strategy for Niemann-Pick diseases based on simultaneous analysis of two phospholipids in blood. In conclusion, the use of LC-MS/MS analysis for endogenous metabolite analysis was found to be useful in the development of diagnostic biomarkers for NPC.