Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review

Shoshana Revel-Vilk, Maria Fuller, Ari Zimran, Shoshana Revel-Vilk, Maria Fuller, Ari Zimran

Abstract

The challenges in the diagnosis, prognosis, and monitoring of Gaucher disease (GD), an autosomal recessive inborn error of glycosphingolipid metabolism, can negatively impact clinical outcomes. This systematic literature review evaluated the value of glucosylsphingosine (lyso-Gb1), as the most reliable biomarker currently available for the diagnosis, prognosis, and disease/treatment monitoring of patients with GD. Literature searches were conducted using MEDLINE, Embase, PubMed, ScienceOpen, Science.gov, Biological Abstracts, and Sci-Hub to identify original research articles relevant to lyso-Gb1 and GD published before March 2019. Seventy-four articles met the inclusion criteria, encompassing 56 related to pathology and 21 related to clinical biomarkers. Evidence for lyso-Gb1 as a pathogenic mediator of GD was unequivocal, although its precise role requires further elucidation. Lyso-Gb1 was deemed a statistically reliable diagnostic and pharmacodynamic biomarker in GD. Evidence supports lyso-Gb1 as a disease-monitoring biomarker for GD, and some evidence supports lyso-Gb1 as a prognostic biomarker, but further study is required. Lyso-Gb1 meets the criteria for a biomarker as it is easily accessible and reliably quantifiable in plasma and dried blood spots, enables the elucidation of GD molecular pathogenesis, is diagnostically valuable, and reflects therapeutic responses. Evidentiary standards appropriate for verifying inter-laboratory lyso-Gb1 concentrations in plasma and in other anatomical sites are needed.

Keywords: Gaucher disease; biomarker; glucosylsphingosine; lyso-Gb1; lysosomal storage disorder; systematic literature review.

Conflict of interest statement

The SZMC Gaucher Unit receives support from Sanofi/Genzyme for participation in the ICGG Registry, from Takeda for the GOS Registry, and Pfizer for TALIAS. S.R.-V. has received research/speaker fees and travel support from Pfizer, Sanofi Genzyme, and Takeda (Shire) and advisory fee from Takeda (Shire) and Prevail therapeutics. M.F. has received travel and research support from Sanofi-Genzyme and Takeda (Shire) A.Z. has received honoraria from Pfizer, Takeda (Shire) and BioEvents, and consultancy fees from Prevail Therapeutics, Avrobio, Insightec and Takeda. Takeda was involved in the concept and design of the study, and had no role in the collection or interpretation of data.

Figures

Figure 1
Figure 1
Catabolic route of glycosphingolipid generation in Gaucher disease [7].
Figure 2
Figure 2
Research milestones culminating in glucosylsphingosine (lyso-Gb1) as a focus of biomarker research.
Figure 3
Figure 3
Literature identification and study selection process for publications reporting on glucosylsphingosine (lyso-Gb1) in Gaucher disease (PRISMA flowchart). a: Three articles reported on roles for lyso-Gb1 in pathophysiology and as a biomarker [26,45,53].

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