UPLC-MS/MS High-Risk Screening for Sphingolipidoses Using Dried Urine Spots.

Area of Science:

• Biochemistry
• Clinical Chemistry
• Mass Spectrometry

Background:

• Early detection of sphingolipidoses is critical for preventing severe complications.
• Dried urine samples (DUS) provide a simpler, non-invasive alternative to liquid urine for sample collection, storage, and transport.

Purpose of the Study:

• To develop and validate a multiplex UPLC-MS/MS method for quantifying 21 lysosphingolipids from DUS for eight sphingolipidoses.
• To establish normal reference values for assessing the clinical utility of the developed methodology.

Main Methods:

• Urine samples were collected on filter paper, eluted, and extracted using solid-phase extraction.
• Quantification was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Main Results:

• Lysosphingolipids in DUS remained stable under various storage conditions for extended periods.
• Elevated levels of specific lysosphingolipids were observed in patients with Fabry and Gaucher diseases compared to controls (p < 0.0001).
• The method demonstrated potential for reliable early detection, particularly for Fabry disease.

Conclusions:

• The developed UPLC-MS/MS method using DUS is a feasible approach for sphingolipidoses.
• This methodology can aid in the early detection, monitoring, and follow-up of patients with these genetic disorders.