Biomarkers in Rare Diseases play a dual and significant role in supporting improved clinical outcomes. In Fabry Disease (FD), the glycosphingolipid globotriaosylceramide (Gb3/GL-3) and its deacylated derivative globotriaosylsphingosine (Lyso-Gb3/Lyso-GL-3) accumulate in different body parts and Lyso-GL-3 is considered the hallmark biomarker for this disease.1

Earlier works have shown that Lyso-GL-3 analysis is an important indicator for identifying Fabry Disease, in particular for females with FD where enzyme activity testing is typically normal. In a recent publication in the Journal of Medical Genetics, Novak et al show that Lyso-GL-3 is a significant risk factor associated with adverse clinical events such as kidney replacement, atrial fibrillation, or cerebrovascular events.

“A specific biomarker could not only fill the diagnostic gap but also improve disease staging and risk stratification as well as support the decision whether a patient should be started on ERT and or if he should be more closely monitored.”

In this paper, Novak explains that Lyso-GL-3 levels do decrease initially with enzyme replacement therapy however in some patients (e.g. with antidrug antibodies), the levels of Lyso-GL-3 will begin to rise again over time. This highlights the importance of measuring biomarker levels during disease diagnosis, prior to treatment initiation, and continually monitoring biomarker levels during treatment.

Read the entire paper at the Journal of Medical Genetics.

[1] Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A 2008;105:2812–7.doi:10.1073/pnas.0712309105pmid: