Glucosylsphingosine (lyso-Gb1) as a Biomarker for Monitoring Treated and Untreated Children with Gaucher Disease

Abstract

The role of glucosylsphingosine (lyso-Gb1), a downstream metabolic product of glucosylceramide, for monitoring treated and untreated children with Gaucher disease (GD) has not yet been studied. We reviewed the clinical charts of 81 children (<18 years), 35 with mild type 1 GD (GD1), 34 with severe GD1 and 12 with type 3 GD (GD3), followed at Shaare Zedek Medical Center between 2014–2018. Disease severity for GD1 was based on genotypes. Forty children (87%) with severe GD1 and GD3 received enzyme replacement therapy (ERT) compared to two children (6%) with mild GD1. Lyso-Gb1 measurements were conducted on dried blood spot samples taken at each clinic visit. Lyso-Gb1 levels were significantly lower in children with mild compared to severe GD1 (p = 0.009). In untreated children, lyso-Gb1 levels were inversely correlated with platelet counts. During follow-up, lyso-Gb1 increased in almost 50% of untreated children, more commonly in younger children. In treated children, lyso-Gb1 levels were inversely correlated with hemoglobin levels. The increase of lyso-Gb1 while receiving ERT, seen in eight children, was partly associated with compliance and weight gain. Lyso-Gb1 seems to be a useful biomarker for monitoring children with GD and should be included in the routine follow-up. Progressive increase in lyso-Gb1 levels in untreated children suggests ERT initiation.

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

“…Four recent studies found that lyso-Gb1 measurement in dried blood spots is useful for monitoring patients with GD [ 126 , 127 , 128 ]. Among 103 untreated adult patients with type 1 GD who were followed up over a median of 20 years, the median lyso-Gb1 in dried blood spots at the last visit was 108.5 ng/mL (normal, <8 ng/mL) [ 126 ].…”

“…Lyso-Gb1 concentrations negatively correlated with platelet count in non-splenectomized patients but not with any other GD-related parameter [ 126 ]. In a separate study, up to 10 years of lyso-Gb1 data (measured in plasma and dried blood spots) from 292 patients enrolled in a single center participating in the Gaucher Outcome Survey registry were analyzed with respect to treatment outcomes [ 127 ]. Most patients had the homozygous N370S genotype and received relatively low doses of ERT [ 127 ].…”

“…In a separate study, up to 10 years of lyso-Gb1 data (measured in plasma and dried blood spots) from 292 patients enrolled in a single center participating in the Gaucher Outcome Survey registry were analyzed with respect to treatment outcomes [ 127 ]. Most patients had the homozygous N370S genotype and received relatively low doses of ERT [ 127 ]. At the time of first lyso-Gb1 assessment, patients on treatment had lower concentrations of plasma lyso-Gb1 than patients who were untreated at that time [ 127 ].…”

Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease

“…They are used as an indicator of disease severity and its response to therapy. Currently, glucosylsphingosine (lyso-Gb1) is used as a more effective alternative to chitotriosidase and CCL18 [113,114].…”

Metabolomic Studies of Lipid Storage Disorders, with Special Reference to Niemann-Pick Type C Disease: A Critical Review with Future Perspectives

“…The plasma biomarker glucosylceramide (GlcCer), and ceramide ratios, have been used in combination with ERT treatment for this condition, with levels significantly decreasing with corresponding treatments in GD 1 patients [44]. Moreover, glucosylsphingosine has also been determined to be a biomarker in dried blood spots (DBS) from children with GD 1 and 3 diseases [47]. Glucosylsphingosine has also proven to have diagnostic potential in other LSDs, further validating its potential as a generalised LSD-specific biomarker [45,46].…”