Work

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

Year: 2024

Type: article

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.

Source: Journal of Clinical Laboratory Analysis

DOI: 10.1002/jcla.25131