Glucosylsphingosine (lyso-Gb1) seems to be a useful biomarker for monitoring disease activity in children with Gaucher disease, helping physicians determine when enzyme replacement therapy should be initiated, a study suggests.
The disease most commonly affects children and teenagers, with almost half of all cases being diagnosed in children before age 10.
The standard of care for Gaucher disease in children has been early intervention with enzyme replacement therapy (ERT). This has led to significant improvements in disease-related symptoms, and a reduction in complications.
In the past, Gaucher was only diagnosed after children presented with symptoms. However, the extensive use of genetic screening now allows doctors to diagnose the disease in many children who don’t yet have symptoms.
In these circumstances, it is important to determine whether ERT should be given and, if so, when it should be initiated. ERT is unnecessary in children who won’t develop any symptoms for many years. However, conversely, other children may develop complications that could have been avoided by early initiation of ERT.
One of the ways to determine which children should be treated is by monitoring the presence of certain biomarkers.
Glucosylsphingosine (lyso-Gb1), a proprietary biomarker developed by Centogene, is a modified form of glucosylceramide. It also is degraded by β-glucocerebrosidase, and thus accumulates in Gaucher patients. Lyso-Gb1 has been shown to be a highly sensitive and specific biomarker for diagnosis and monitoring of adults with Gaucher disease.
However, its use as a biomarker in children has not yet been investigated.
Therefore, researchers explored the role of lyso-Gb1 for monitoring disease status in a group of 81 treated and untreated children with the disease. Among them, 35 patients had mild type 1 Gaucher disease (GD1), 34 had severe GD1, and 12 had type 3 disease (GD3).
Most children (87%) who had either severe GD1 or GD3 received ERT, while only 6% of children with mild GD1 received the same treatment.
Researchers conducted lyso-Gb1 measurements using dried blood spot samples taken at each clinic visit. They found that lyso-Gb1 levels were significantly lower in children with mild GD1 compared with severe GD1. However, there were no significant differences between children with mild GD1 and GD3.
In untreated children, lyso-Gb1 inversely correlated with platelet counts, and increased by almost half during follow-up, particularly in young children. In treated children, lyso-Gb1 correlated with hemoglobin levels, and decreased in 57% of patients who were not receiving treatment at first examination.
For those on ERT at first examination, 56% had their lyso-Gb1 levels decrease during follow-up. Eight of these children had their levels rise — which researchers attributed to lack of treatment compliance and weight gain.
“The correlations found between lyso-Gb1 levels and disease severity as well as the changes in levels with and without therapy support the importance of using this biomarker in monitoring children with GD [Gaucher disease], both untreated and treated, for the need to start treatment and to follow the response to therapy, respectively,” the researchers said.
“The progressive increase in lyso-Gb1 levels in untreated GD children suggests that these patients should receive enzyme replacement therapy,” Ari Zimran, MD, a highly recognized expert on Gaucher disease and contributing author of the study, said in a press release.
“This international study has demonstrated a correlation between lyso-Gb1 levels and disease severity among children suffering from Gaucher Disease, and the importance of using this biomarker in monitoring treated and untreated children,” said Zimran, of the Shaare Zedek Medical Center at Hebrew University in Jerusalem,
“We strongly recommend including lyso-GB1 in the routine follow-up of all children with GD and a progressive increment in lyso-Gb1 should lead to consideration of ERT in untreated children or to a dose increase in treated children,” the investigators concluded.