Evaluation of Lysosphingolipid Analysis in the Diagnosis of Lysosomal Storage Disorders

Objectives: Lysosomal storage disorders (LSD) are a group of inherited inborn errors of metabolism characterized by a deficiency of a lysosomal enzyme. In patients with suspected lipid storage disorders, confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and molecular genetic studies. New methods have been developed to measure lysosphingolipids and may represent a rapid first-tier screening test for the evaluation of LSD. This study evaluated the lysosphingolipid screening test results of patients suspected of having an LSD.

Methods: EDTA plasma samples were used for lysosphingolipid analysis by LC-MS/MS after extraction with organic solvents containing an internal standard (ESP+ ionisation using BEH C18, 2.1× 50 mm, 1.7 μm column in MRM mode). The results were calculated from the calibration curve at different concentrations prepared in-house for each sphingolipid and evaluated as nmol/L.

Results: Among the 107 patients admitted to the Department of Pediatric Metabolism of Ankara City Hospital suspected of having an LSD between January 2021 and January 2022, 41 Patients were girls and 66 were boys. Five patients with significantly higher lysosphingolipid levels were diagnosed with an LSD by molecular genetic analysis.

Conclusion: Recently, many biochemical markers have been identified that aid the diagnosis of sphingolipidoses. In our study, lysosphingolipid elevation was detected in 5 patients suspected of having an LSD and a definitive diagnosis was reached by genetic analysis. Our data support recent evidence for the primary role of lysosphingolipids in the diagnosis of sphingolipidosis and these biomarkers could be used
for diagnosis and treatment monitoring in the future.