Lyso-Gb1- in search of a highly specific biomarker for Gaucher disease

Abstract

Gaucher disease (GD) is a rare, autosomal recessive disorder, belonging to the group of lysosomal storage diseases
(LSDs). The essence of the disease is a decrease in glucocerebrosidase activity, leading to an accumulation of glucosylceramide in the liver, spleen, bone marrow, bones, and other organs. Gaucher disease presents with a wide range
of phenotypic variations and is classified into three types based on the presence of neurological symptoms. Due to
the heterogeneous course of the disease, accurate diagnosis is often delayed by many years. Various biomarkers
are useful in diagnosing, monitoring progression and treating this disease, such as angiotensin-converting enzymes,
serum ferritin, CCL18 and chitotriosidase. The search for a more specific and sensitive biomarker has led to the identification of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1).

Lyso-Gb1, as a biomarker, is easily measurable in clinical samples, including dried blood spots. It has diagnostic and
predictive value and also reflects therapeutic response. A rapid and significant reduction in lyso-Gb1 concentrations
in plasma or cerebrospinal fluid following treatment has been reported by many researchers. The levels of lyso-Gb1
decrease during effective treatment, which allows for a determination of whether a patient is responding to treatment,
and can indicate the ineffectiveness of therapy before clinical consequences appear. It has been demonstrated
that biomarker levels correlate with improvements in disease parameters, including liver volume, spleen volume,
hemoglobin and platelet counts. This indicates that a low plasma lyso-Gb1 concentration correlates with a higher
therapeutic success rate.