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Reductions in Glucosylsphingosine

Deborah Elstein Björn Mellgard, PhD MD Quinn Dinh, MD Yongchang Qiu, PhD Dr. rer. nat. Claudia Cozma, MD Sabrina Eichler, PhD Tobias Böttcher, PhD Ari Zimran, MD Lan Lan
August 19, 2017

Reductions in Glucosylsphingosine (lyso-Gb1) in Treatment-Naïve and Previously Treated Patients Receiving Velaglucerase Alfa for Type 1 Gaucher Disease

Molecular Genetics and Metabolism (2017),


Gaucher disease (GD), an autosomal recessive lipid storage disorder, arises from mutations in the GBA1 (β- glucocerebrosidase) gene, resulting in glucosylceramide accumulation in tissue macrophages. Lyso-Gb1 (glucosylsphingosine, lyso-GL1), a downstream metabolic product of glucosylceramide, has been identified as a promising biomarker for the diagnosis and monitoring of patients with GD. This retrospective, exploratory analysis of data from phase 3 clinical trials of velaglucerase alfa in patients with type 1 GD evaluated the potential of lyso-Gb1 as a specific and sensitive biomarker for GD. A total of 22 treatment-naïve patients and 21 patients previously treated with imiglucerase (switch patients) were included in the analysis. Overall, demographics between the two groups were similar. Mean lyso-Gb1 concentrations were reduced by 302.2 ng/mL from baseline to week 209 in treatment-naïve patients and by 57.3 ng/mL from baseline to week 161 in switch patients, corresponding to relative reductions of 82.7% and 52.0%, respectively. In both the treatment-naïve and switch groups, baseline mean lyso-Gb1 was higher for patients with at least one N370S mutation (363.9 ng/mL and 90.7 ng/mL, respectively) than for patients with non-N370S mutations (184.6 ng/mL and 28.3 ng/mL, respectively). Moderate correlations between decreasing lyso-Gb1 levels and increasing platelet counts, and with decreasing spleen volumes, were observed at some time points in the treatment-naïve group but not in the switch group. These findings support the utility of lyso-Gb1 as a sensitive and reliable biomarker for GD, and suggest that quantitation of this biomarker could serve as an indicator of disease burden and response to treatment.