# High-Resolution Mass Spectrometry Method for Targeted Screening and Monitoring of Fabry, Gaucher and ASMD Using Dried Blood Spots and Capitainers: Impact of Sample Matrix on Measurement Results

## TL;DR

This paper introduces a high-resolution mass spectrometry method for diagnosing and monitoring three lysosomal storage diseases using small blood samples collected on dried blood spots or Capitainers.

## Contribution

A validated, sensitive, and clinically applicable mass spectrometry method for Fabry, Gaucher, and ASMD using DBS and Capitainers is introduced.

## Key findings

- The method was validated for reproducibility, linearity, and lower limit of quantification according to CLSI guidelines.
- Capitainers showed improved validation parameters compared to dried blood spots.
- All patient samples were detected accurately with no ambiguity.

## Abstract

The sphingolipidoses Fabry disease, Gaucher disease and Acid sphingomyelinase deficiency (ASMD) are the three most common lysosomal storage diseases for which treatment is currently available. Timely diagnosis with estimation of the disease severity and possibilities of follow-up of patients, whether or not under therapy, is crucial for providing good care and for the prevention of possible lethal complications. With this research we provide an efficient and sensitive detection method; its implementation in clinical practice could optimize the diagnosis and follow-up of patients with Gaucher, Fabry and ASMD. This detection method on dried blood spots (DBS) was validated according to the international Clinical and Laboratory Standards Institute (CLSI) guidelines, looking at reproducibility, linearity, carry-over and lower limit of quantification. Analogously, validation and subsequent comparison of the method validation results using another matrix, the Capitainer blood sampling cards (Capitainers), was fulfilled. The results showed that this detection method is fully applicable clinically when using DBS as well as Capitainers. In addition, even additional improvements of some validation parameters were found when using the Capitainers. Twenty-six patient samples and fifteen healthy samples were analyzed for case finding control. All patient cases were detected without ambiguity. We present a high-resolution mass spectrometry method that provides an accurate analysis for targeted screening, aiming for improved/accelerated diagnosis when added in the diagnostic pathway and monitoring of Fabry, Gaucher and ASMD in DBS as well as in Capitainers, with the main advantages of a small volume of blood samples, guaranteeing stability and easy transportation from the collection site to the laboratory.