sphingosine-phosphorylcholine and Niemann-Pick-Disease--Type-B

Acid sphingomyelinase deficiency (ASMd, Niemann-Pick disease A/B) and Niemann-Pick type C disease (NPC) share core clinical symptoms. Initial diagnostic discrimination of these two rare lysosomal storage diseases is thus difficult. As sphingomyelin accumulates in ASMd as well as NPC, lysosphingomyelin (sphingosylphosphorylcholine) and its m/z 509 analog were suggested as biomarkers for both diseases. Herein we present results of simultaneous LC-ESI-MS/MS measurements of lysosphingomyelin and lysosphingomyelin 509 in plasma and dried blood spots (DBS) collected from ASMd and NPC patients and suggest that the plasma but not DBS levels of the two analytes allow differential biochemical screening of ASMd and NPC.

Topics: Biomarkers; Case-Control Studies; Chromatography, Liquid; Dried Blood Spot Testing; Humans; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type B; Niemann-Pick Disease, Type C; Phosphorylcholine; Spectrometry, Mass, Electrospray Ionization; Sphingosine; Tandem Mass Spectrometry

Niemann-Pick disease type B (NPD-B) is caused by a partial deficiency of acid sphingomyelinase activity and results in the accumulation of lysosomal sphingomyelin (SPM) predominantly in macrophages. Notably, SPM is not significantly elevated in the plasma, whole blood, or urine of NPD-B patients. Here, we show that the de-acylated form of sphingomyelin, lyso-SPM, is elevated approximately 5-fold in dried blood spots (DBS) from NPD-B patients and has no overlap with normal controls, making it a potentially useful biomarker.

Topics: Blood Cells; Case-Control Studies; Dried Blood Spot Testing; Humans; Lysosomes; Macrophages; Niemann-Pick Disease, Type B; Phosphorylcholine; Sphingomyelin Phosphodiesterase; Sphingosine