Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study.
Adolescent
Adult
Aged
Biomarkers
/ blood
Child
Child, Preschool
Chromatography, Liquid
/ methods
Dried Blood Spot Testing
/ methods
Female
Humans
Infant
Infant, Newborn
Lysosomal Storage Diseases
/ blood
Male
Middle Aged
Plasma
/ chemistry
Reference Values
Reproducibility of Results
Sensitivity and Specificity
Sphingolipidoses
/ blood
Sphingolipids
/ analysis
Tandem Mass Spectrometry
/ methods
Fabry disease
Gaucher disease
Krabbe disease
Niemann-Pick type A/B disease
Niemann-Pick type C disease
biomarkers
dried blood spot (DBS)
gangliosidosis GM1
gangliosidosis GM2
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
26 Nov 2019
26 Nov 2019
Historique:
received:
06
12
2018
accepted:
14
04
2019
pubmed:
16
5
2019
medline:
18
9
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
Background Lysosphingolipids, the N-deacylated forms of sphingolipids, have been identified as potential biomarkers of several sphingolipidoses, such as Gaucher, Fabry, Krabbe and Niemann-Pick diseases and in GM1 and GM2 gangliosidoses. To date, different methods have been developed to measure various lysosphingolipids (LysoSLs) in plasma. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for a simultaneous quantification of LysoSLs (HexSph, LysoGb3, LysoGM1, LysoGM2, LysoSM and LysoSM509) in dried blood spot (DBS). This LC-MS/MS method was used to compare the levels of LysoSLs in DBS and plasma in both affected patients and healthy controls. Methods Lysosphingolipids were extracted from a 3.2 mm diameter DBS with a mixture of methanol:acetonitrile:water (80:15:5, v/v) containing internal stable isotope standards. Chromatographic separation was performed using a C18 column with a gradient of water and acetonitrile both with 0.1% formic acid in a total run time of 4 min. The compounds were detected in the positive ion mode electrospray ionization (ESI)-MS/MS by multiple reaction monitoring (MRM). Results The method was validated on DBS to demonstrate specificity, linearity, lowest limit of quantification, accuracy and precision. The reference ranges were determined in pediatric and adult populations. The elevated levels of LysoSLs were identified in Gaucher disease (HexSph), Fabry disease (LysoGb3), prosaposin deficiency (HexSph and LysoGb3) and Niemann-Pick disease types A/B and C (LysoSM and LysoSM509). The correlation in the levels between DBS and plasma was excellent for LysoGb3 and HexSph but poor for LysoSM and LysoSM509. Conclusions Despite the fact that plasma LysoSLs determination remains the gold standard, our LC-MS/MS method allows a rapid and reliable quantification of lysosphingolipids in DBS. The method is a useful tool for the diagnosis of different sphingolipidoses except for Niemann-Pick type C.
Identifiants
pubmed: 31091195
doi: 10.1515/cclm-2018-1301
pii: cclm-2018-1301
doi:
Substances chimiques
Biomarkers
0
Sphingolipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1863-1874Commentaires et corrections
Type : CommentIn
Références
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