title: Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS.
abstract: BACKGROUND
  Lysosphingolipids (LysoSLs) are derivatives of sphingolipids which have lost the amide-linked acyl chain. More recently, LysoSLs have been identified as storage compounds in several sphingolipidoses, including Gaucher, Fabry and Niemann-Pick diseases. To date, different methods have been developed to measure each individual lysosphingolipid in plasma. This report describes a rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of several LysoSLs in plasma.
  
  
  METHODS
  We analyzed the following compounds: hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM) and lysosphingomyelin-509 (LysoSM-509). The sample preparation requires only 100 μL of plasma and consists of an extraction with a mixture of MeOH/acetone/H2O (45:45:10, v/v).
  
  
  RESULTS
  The method validation showed high sensitivity, an excellent accuracy and precision. Reference ranges were determined in healthy adult and pediatric population. The results demonstrate that the LC-MS/MS method can quantify different LysoSLs and can be used to identify patients with Fabry (LysoGb3), Gaucher and Krabbe (HexSph) diseases, prosaposine deficiency (LysoGb3 and HexSph), and Niemann-Pick disease types A/B and C (LysoSM and LysoSM-509).
  
  
  CONCLUSIONS
  This LC-MS/MS method allows a rapid and simultaneous quantification of LysoSLs and is useful as a biochemical diagnostic tool for sphingolipidoses.
authors.forename: Giulia
authors.initials: G
authors.lastname: Polo
authors.forename: Alessandro P
authors.initials: AP
authors.lastname: Burlina
authors.forename: Thilini B
authors.initials: TB
authors.lastname: Kolamunnage
authors.forename: Michele
authors.initials: M
authors.lastname: Zampieri
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: Pietro
authors.initials: P
authors.lastname: Strisciuglio
authors.forename: Martina
authors.initials: M
authors.lastname: Zaninotto
authors.forename: Mario
authors.identifier: http://orcid.org/0000-0002-0270-1711
authors.initials: M
authors.lastname: Plebani
authors.forename: Alberto B
authors.initials: AB
authors.lastname: Burlina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results; D013106:Sphingolipidoses / Q000097:blood / Q000175:diagnosis*; D013107:Sphingolipids / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D013107:Sphingolipids