Plasma lipids are altered in Gaucher disease: biochemical markers to evaluate therapeutic intervention.

Enzyme replacement therapy has been in clinical practice for the non-neuronopathic form of Gaucher disease for 15 years. However, the wide phenotypic variability in this disorder poses challenges to clinicians to assess patient severity and disease progression in order to effectively manage patients. Once therapy is initiated, methods to monitor the complex biochemical changes associated with the disease, and the response of these changes to therapy, are required in order to tailor therapy regimens to individual patients. We have evaluated the suitability of plasma sphingolipids and phospholipids as biochemical markers of disease burden and the efficacy of therapy to reduce that burden. Over 60 lipid species were measured using electrospray ionization-tandem mass spectrometry in plasma from controls and Gaucher patients, pre- and post-therapy. Glucosylceramide, molecular species of phosphatidylglycerol and G(M3) ganglioside were elevated in Gaucher disease, whereas species of ceramide, dihexosylceramide and sphingomyelin were decreased. Multivariate analysis enabled us to calculate the combined response of these lipids to therapy in Gaucher patients and correlate them with patient severity. Plasma lipids are proposed to be useful biomarkers for Gaucher disease.