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

doi:10.1515/cclm-2016-0340

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

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	403-414
Number of pages	12
Journal	Clinical Chemistry and Laboratory Medicine
Volume	55
Issue number	3
DOIs	https://doi.org/10.1515/cclm-2016-0340
Publication status	Published - Aug 17 2016

Keywords

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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Diagnosis of sphingolipidoses : a new simultaneous measurement of lysosphingolipids by LC-MS/MS. / Polo, Giulia; Burlina, Alessandro P.; Kolamunnage, Thilini B; Zampieri, Michele; Dionisi-Vici, Carlo; Strisciuglio, Pietro; Zaninotto, Martina; Plebani, Mario; Burlina, Alberto B.

In: Clinical Chemistry and Laboratory Medicine, Vol. 55, No. 3, 17.08.2016, p. 403-414.

Research output: Contribution to journal › Article › peer-review

Polo, Giulia ; Burlina, Alessandro P. ; Kolamunnage, Thilini B ; Zampieri, Michele ; Dionisi-Vici, Carlo ; Strisciuglio, Pietro ; Zaninotto, Martina ; Plebani, Mario ; Burlina, Alberto B. / Diagnosis of sphingolipidoses : a new simultaneous measurement of lysosphingolipids by LC-MS/MS. In: Clinical Chemistry and Laboratory Medicine. 2016 ; Vol. 55, No. 3. pp. 403-414.

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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.",

keywords = "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",

author = "Giulia Polo and Burlina, {Alessandro P.} and Kolamunnage, {Thilini B} and Michele Zampieri and Carlo Dionisi-Vici and Pietro Strisciuglio and Martina Zaninotto and Mario Plebani and Burlina, {Alberto B.}",

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doi = "10.1515/cclm-2016-0340",

language = "English",

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T1 - Diagnosis of sphingolipidoses

T2 - a new simultaneous measurement of lysosphingolipids by LC-MS/MS

AU - Polo, Giulia

AU - Burlina, Alessandro P.

AU - Kolamunnage, Thilini B

AU - Zampieri, Michele

AU - Dionisi-Vici, Carlo

AU - Strisciuglio, Pietro

AU - Zaninotto, Martina

AU - Plebani, Mario

AU - Burlina, Alberto B.

PY - 2016/8/17

Y1 - 2016/8/17

N2 - 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.

AB - 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.

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KW - Adult

KW - Aged

KW - Biomarkers

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Chromatography, Liquid

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Middle Aged

KW - Reference Values

KW - Reproducibility of Results

KW - Sphingolipidoses

KW - Sphingolipids

KW - Tandem Mass Spectrometry

KW - Young Adult

KW - Comparative Study

KW - Journal Article

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DO - 10.1515/cclm-2016-0340

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JO - Clinical Chemistry and Laboratory Medicine

JF - Clinical Chemistry and Laboratory Medicine

SN - 1434-6621

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