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.

journal_name

Clin Chem Lab Med

authors

Polo G,Burlina AP,Kolamunnage TB,Zampieri M,Dionisi-Vici C,Strisciuglio P,Zaninotto M,Plebani M,Burlina AB

doi

10.1515/cclm-2016-0340

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

403-414

issue

3

eissn

1434-6621

issn

1437-4331

pii

/j/cclm.ahead-of-print/cclm-2016-0340/cclm-2016-03

journal_volume

55

pub_type

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