The Human Plasma Lipidome

The Human Plasma LipidomeTo the Editor: In their review, Quehenberger and Dennis (Nov. 10 issue) 1 describe plasma lipids implicated in Gaucher's disease.Although they could not possibly mention every lipid, we believe it is worth commenting on the cationic amphiphilic glycolipid globotriaosylsphingosine (lyso-Gb3) and its contribution to a better understanding of the pathogenesis and monitoring of Fabry's disease.High plasma concentrations of lyso-Gb3 were observed in patients with this disease, 2 and these levels correlated with several of its manifestations 3 and decreased in response to enzyme-replacement therapy.4,5 Furthermore, lyso-Gb3 promoted vascular smooth-muscle cell proliferation 2 as well as transforming growth factor-β1-mediated synthesis of extracellular matrix components in cultured podocytes at concentrations found in the plasma.6 In Fabry's disease, vascular smooth-muscle cells and podocytes are cell targets, whereas fibrosis is a key feature of organ injury.The novelty, from a pathogenetic point of view, resides in the fact that a soluble mediator promotes cell injury in a disease long thought to be the result of intracel-The New England Journal of Medicine correspondence lular lipid accumulation within lysosomes.This paradigm shift may have therapeutic implications.