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. 2025 Jan;39(1):e25131.
doi: 10.1002/jcla.25131. Epub 2024 Dec 27.

Lysosphingolipid Quantitation in Plasma and Dried-Blood Spots Using Targeted High-Resolution Mass Spectrometry

Franklin Ducatez  1   2 , Wladimir Mauhin  3 , Jules Ottaviani  1 , Thomas Plichet  1 , Carine Pilon  1 , Olivier Lidove  3 , Fréderic Barbey  4 , Régine Perrichot  5 , Sabrina Vergnaud  6 , Marc G Berger  7   8 , Juliette Berger  7   8 , Nadia Belmatoug  9 , Yann Nadjar  10 , Foudil Lamari  11 , Esther Noel  12 , Stéphane Marret  2 , Soumeya Bekri  1 , Abdellah Tebani  1
Affiliations

Lysosphingolipid Quantitation in Plasma and Dried-Blood Spots Using Targeted High-Resolution Mass Spectrometry

Franklin Ducatez et al. J Clin Lab Anal. 2025 Jan.

Abstract

Background: Sphingolipidoses are rare inherited metabolic diseases belonging to lysosomal diseases. Early and accurate diagnosis is crucial for effective management and treatment. In this study, we aimed to develop a robust method to accelerate the diagnosis of these sphingolipidoses using dried blood spots and plasma.

Method: We employed high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS) to analyze 6 lysosphingolipids (GlcSph/Psychosine, LysoGb3, LysoSM, LysoSM509, LysoGM1, and LysoGM2) on dried blood spots and plasma samples. The method was used to measure the lysosphingolipid levels in a group of 30 control subjects and 204 samples from patients with sphingolipidoses (61 dB and 143 plasma) including Fabry, Gaucher, GM2 Gangliodosis, Niemann-Pick type A/B, and Niemann-Pick type C.

Results: The developed multiplex LC-HRMS method demonstrated linearity, precision, and quantification performances particularly for GlcSph/Psychosine and LysoGb3 on samples including controls and patients with sphingolipidoses. LysoSM showed recovery variability, wherease LysoGM1 and LysoGM2 showed higher matrix effect.

Conclusion: Our study presents a high-resolution mass spectrometry method along with the established cutoff values, providing a valuable tool for targeted screening, accurate diagnosis, and monitoring sphingolipidoses. Furthermore, DBS showed reliable results that lay the path to a broader adoption for screening these diseases.

Keywords: dried blood spot; lysosomal diseases; mass spectrometry; screening; sphingolipids.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overview of the biochemical components of lysosphingolipids biomarkers and their respective disease.
FIGURE 2
FIGURE 2
Metabolic mapping of the lysosphingolipids biomarkers and their respective diseases.
FIGURE 3
FIGURE 3
Overview of previously reported methods for lysosphingolipids measurements.
FIGURE 4
FIGURE 4
Example of a chromatogram.
FIGURE 5
FIGURE 5
Overview of patient lysosphingolipids levels in plasma and DBS samples.
See this image and copyright information in PMC

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