Lysosphingolipid urine screening test using mass spectrometry for the early detection of lysosomal storage disorders

Bioanalysis. 2022 Mar;14(5):289-306. doi: 10.4155/bio-2021-0259. Epub 2022 Feb 4.

Abstract

Background: Sphingolipidoses are caused by a defective sphingolipid catabolism, leading to an accumulation of several glycolipid species in tissues and resulting in neurotoxicity and severe systemic manifestations. Methods & results: Urine samples from controls and patients were purified by solid-phase extraction prior to the analysis by ultra-high-performance liquid chromatography (UPLC) combined with MS/MS. A UPLC-MS/MS method for the analysis of 21 urinary creatinine-normalized biomarkers for eight diseases was developed and validated. Conclusion: Considering the growing demand to identify patients with different sphingolipidoses early and reliably, this methodology will be applied for high-risk screening to target efficiently patients with various sphingolipidoses.

Keywords: analog; biomarker; creatinine; lysosomal storage diseases; lysosphingolipid; screening; sphingolipidosis; tandem mass spectrometry; ultra-high-performance liquid chromatography; urine.

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / methods
  • Humans
  • Lysosomes
  • Solid Phase Extraction*
  • Sphingolipids
  • Tandem Mass Spectrometry* / methods

Substances

  • Sphingolipids