Determination of 7-ketocholesterol in plasma by lc-ms for rapid diagnosis of acid smase-deficient niemann-pick disease

Abstract

Acid sphingomyelinase (ASMase)-deficient Niemann- Pick disease (NPD) is caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene, resulting in accumulation of sphingomyelin in the lysosomes and secondary changes in cholesterol metabolism. We hypothesized that the oxidation product of cholesterol, 7-ketocholesterol (7-KC), might increase in the plasma of patients with ASMase-deficient NPD. In this study, a rapid and nonderivatized method of measurement of plasma 7-KC by liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was developed. Plasma samples from healthy subjects, patients with ASMase-deficient NPD, nonaffected ASMasedeficient NPD heterozygotes, Niemann-Pick type C (NPC) disease, glycogen storage disorder type II (GSDII), Gaucher disease (GD), mucopolysaccharidosis type II (MPSII), Krabbe disease (KD), and metachromatic leukodystrophy (MLD) were tested retrospectively. Markedly elevated 7-KC was found in patients with ASMase-deficient NPD and NPC disease that showed significant differences from ASMasedeficient NPD heterozygotes; patients with GSDII, GD, MPSII, KD, and MLD; and normal controls. The analysis of plasma 7-KC by LC-MS/MS offers the first simple, quantitative, and highly sensitive method for detection of ASMase-deficient NPD and could be useful in the diagnosis of both ASMasedeficient NPD and NPC disease. -Lin, N., H. Zhang, W. Qiu, J. Ye, L. Han, Y. Wang, and X. Gu. Determination of 7-ketocholesterol in plasma by LC-MS for rapid diagnosis of acid SMase-deficient Niemann-Pick disease. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc..