Searching, Structural Determination, and Diagnostic Performance Evaluation of Biomarker Molecules for Niemann–Pick Disease Type C Using Liquid Chromatography/Tandem Mass Spectrometry

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive disorder that is characterized by progressive neuronal degeneration. Patients with NPC have a wide age of onset and various clinical symptoms. Therefore, the discovery and diagnosis of NPC are very difficult. Mass Spectrometry Advance Publication 2 Conventional laboratory tests are complicated and time consuming. In this context, biomarker searches have recently been performed. Our research group has previously also investigated NPC biomarkers based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) and related techniques. To identify biomarker candidates, nontargeted analysis with highresolution MS and MS/MS scanning is commonly used. Structural speculation has been performed using LC/MS/MS fragmentation and chemical derivatization, while identification is performed by matching authentic standards and sample specimens. Diagnostic performance evaluation was performed using the validated LC/MS/MS method and analysis of samples from patients and control subjects. NPC biomarkers, which have been identified and evaluated in terms of performance, are various classes of lipid molecules. Oxysterols, cholenoic acids, and conjugates are cholesterol-derived molecules detected in the blood or urine. Plasma lyso-sphingolipids are biomarkers for both NPC and other lysosomal diseases.N-palmitoyl-O-phosphocholine-serine is a novel class of lipid biomarkers for NPC. This article reviews biomarkers for NPC and the analysis methods employed to that end.

Global Proteomics for Identifying the Alteration Pathway of Niemann–Pick Disease Type C Using Hepatic Cell Models

“…On the other hand, this enrichment analysis did not show any term associated with liver damage in either the GO or KEGG. In addition, many studies have been published regarding metabolic alterations, and we focused on lipid metabolism and reported its use as a diagnostic biomarker [4][5][6][7]. Amino acid alterations were reported by other groups [127,128].…”

“…Niemann-Pick disease type C (NPC) is a progressive and life-limiting autosomal recessive disorder characterized by progressive neurodegeneration [1][2][3]. Due to the development of laboratory medicines for NPC [2,[4][5][6][7][8][9], the number of NPC patients is increasing, and the current estimated prevalence is approximately 1/100,000 [10]. NPC is caused by mutations in NPC1 or NPC2.…”

“…Hepatosplenomegaly and cholestasis are typical symptoms, and many patients develop various neurodegenerative disorders depending on their age [1]. Disease prognosis is generally improved when treatment begins earlier [18]; therefore, earlier diagnosis is desired, and a number of clinical biomarkers have been developed for the early discovery of this condition [4][5][6][7]. Since 2010, oxysterols [19,20], lysosphingomyelin [14,21], N-palmitoyl-O-phosphocholine-serine [22][23][24][25] (previously called Lyso-SM-509), and abnormal bile acids containing conjugates [8,9,[26][27][28][29][30][31][32][33] have been reported as biomarkers of NPC.…”

Analysis of Metabolic Changes in Endogenous Metabolites and Diagnostic Biomarkers for Various Diseases Using Liquid Chromatography and Mass Spectrometry

“…LC/MS/MS is used to identify and quantify several lipid metabolites that have been reported as potential biomarkers for NPC. [48][49][50][51] 2.1.1. Biomarkers Development of Urinary Abnormal Cholesterol Urine Using LC/MS/MS…”