1. Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Prof. Arndt Rolfs, MD 1 Anne Katrin Giese, MD 1 Ulrike Grittner, PhD 2 Daniel Mascher, PhD 3 Deborah Elstein 4 Ari Zimran, MD 4 Tobias Böttcher, PhD 1 Jan Lukas, PhD 1 Rayk Hübner 1 Uta Gölnitz, MD 5 Anja Röhle 5 Ales Dudesek, MD 1 Wolfgang Meyer, MD 6 Matthias Wittstock, MD 1 Prof. Hermann Mascher 3
1 University of Rostock 2 Charité-University, Berlin 3 Pharm-analyt Labor GmbH 4 Shaare Zedek Medical Center (SZMC), Jerusalem 5 CENTOGENE AG 6 Queen Mary University of London
November 20, 2013

PLoS ONE 8(11): e79732. doi:10.1371/journal.pone.0079732

Background: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient bglucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.

Methodology: Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).

Findings: Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.

Interpretation: In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD.