Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS

Giulia Polo, Alessandro P. Burlina, Thilini B Kolamunnage, Michele Zampieri, Carlo Dionisi-Vici, Pietro Strisciuglio, Martina Zaninotto, Mario Plebani, Alberto B. Burlina

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)403-414
Number of pages12
JournalClinical Chemistry and Laboratory Medicine
Issue number3
Publication statusPublished - Aug 17 2016


  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chromatography, Liquid
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Reference Values
  • Reproducibility of Results
  • Sphingolipidoses
  • Sphingolipids
  • Tandem Mass Spectrometry
  • Young Adult
  • Comparative Study
  • Journal Article


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