Rapid, single-phase extraction of glucosylsphingosine from plasma: A universal screening and monitoring tool

• A simple assay to measure plasma glucosylsphingosine for Gaucher disease
• The assay is 100% sensitive and specific.
• This assay is applicable for all patients regardless of chitotriosidase status.
• This assay is recommended for Gaucher disease diagnosis and biochemical monitoring.

BackgroundGlucosylsphingosine (GluSph) has emerged as a biomarker for the inherited metabolic disorder, Gaucher disease (GD). We developed a simple laboratory test to measure plasma GluSph and show that elevated GluSph is diagnostic for GD as well as informing on disease burden for monitoring patients on treatment.MethodsGluSph was measured from a single-phase total lipid extraction of 0.01 mL of plasma by liquid chromatography–electrospray ionisation–tandem mass spectrometry and concentrations extrapolated from a seven point standard curve (0.04 to 20 pmoL). A total of 1464 samples were tested and longitudinal assessment of an additional 20 GD patients.ResultsAll patients with GD had elevated GluSph compared to unaffected controls and 16 other metabolic disorders. GluSph was also slightly elevated in three patients with Krabbe disease but not at concentrations to confuse a GD diagnosis. GluSph correlated with chitotriosidase in the majority of GD patients on treatment who were informative for this marker.ConclusionsGluSph can be easily measured from 0.01 mL of plasma and is useful as a diagnostic marker for GD with the current platform suited to high-throughput screening. It outperforms other GD biomarkers for biochemical monitoring of patients receiving enzyme replacement therapy for all individuals.