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

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.