title: Rapid, single-phase extraction of glucosylsphingosine from plasma: A universal screening and monitoring tool.
abstract: BACKGROUND
  Glucosylsphingosine (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.
  
  
  METHODS
  GluSph 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.
  
  
  RESULTS
  All 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.
  
  
  CONCLUSIONS
  GluSph 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.
authors.affiliation: Genetics and Molecular Pathology, SA Pathology [at Women's and Children's Hospital], 72 King William Road, North Adelaide, South Australia 5006, Australia; Department of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: maria.fuller@adelaide.edu.au.
authors.forename: Maria
authors.initials: M
authors.lastname: Fuller
authors.affiliation: Department of Clinical Haematology, Royal Melbourne Hospital and Department of Medicine, Australia; University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.affiliation: Genetics and Molecular Pathology, SA Pathology [at Women's and Children's Hospital], 72 King William Road, North Adelaide, South Australia 5006, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Stark
authors.affiliation: Genetics and Molecular Pathology, SA Pathology [at Women's and Children's Hospital], 72 King William Road, North Adelaide, South Australia 5006, Australia; Department of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D005776:Gaucher Disease / Q000097:blood* / Q000175:diagnosis*; D057166:High-Throughput Screening Assays; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000097:blood* / Q000175:diagnosis*; D011609:Psychosine / Q000031:analogs & derivatives* / Q000097:blood / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D011609:Psychosine; C035742:sphingosyl beta-glucoside
keywords: Biomarker; Diagnosis; Enzyme replacement therapy; Gaucher disease; Glucosylsphingosine; Mass spectrometry