A specific set of small RNA molecules in the blood can help diagnose Fabry disease and monitor response to therapy, according to recent findings.
The study, “A pilot study of circulating microRNAs as potential biomarkers of Fabry disease” was published in the journal Oncotarget.
Fabry disease is a rare genetic disorder that prevents the body from making an enzyme called alpha-galactosidase A (GLA).
This enzyme is responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3) into building blocks that the body’s cells can use. When these fat molecules are not broken down due to lack of alpha-galactosidase, they accumulate inside the cells and cause damage.
More than 900 genetic mutations in the GLA gene — which encodes for the alpha-galactosidase A enzyme — have been linked to Fabry disease. However, there is little evidence about the association between genetics and differences in disease severity and presentation.
In people from the same family (who carry the same genetic background), the disease can manifest with different symptoms, from a severe classic presentation to a completely asymptomatic pattern.
This variability relies on residual GLA enzymatic activity plus genetic and environmental factors.
As a result, tools that may help predict patient outcomes and responses to treatment would ultimately improve care and disease management, as well as enable appropriate genetic counseling.
To date, the most efficient diagnostic method is to determine residual GLA enzyme activity and conduct a genetic analysis. In addition, an evaluation of the levels of Gb3 and lysoGb3 have been used as biomarkers of Fabry disease.
Still, none of these methods can effectively distinguish between asymptomatic and symptomatic individuals among male or female patients.
Now, a team of Italian researchers assessed the diagnostic potential of microRNA molecules as biomarkers of Fabry disease.
MicroRNAs are tiny RNA molecules that can regulate the levels of both genes and proteins. They are known to be important contributors for the normal balance of cell function, and when deregulated can contribute toward disease worsening.
Researchers analyzed the levels of microRNA molecules in plasma samples collected from 30 Fabry patients, 20 healthy volunteers, and 10 people with a heart condition. Among Fabry patients, 10 had been treated with enzyme replacement therapies (ERT) and the others had no prior treatment.
Ten specific microRNAs were either present in higher or lower amounts (at least by 1.5 times) in Fabry patients compared to healthy controls, and were found to be associated with the disease.
These molecules allowed researchers to differentiate individuals who had the disease from those who did not with a high degree of sensitivity and specificity.
Researchers then compared Fabry patients’ levels of these 10 microRNAs to those of people with similar symptoms, but due to unrelated disorders. Four of the 10 microRNA molecules were able to effectively differentiate between each patient group.
In Fabry disease patients undergoing ERT, two of these four microRNA molecules were reduced to levels close to those of healthy controls.
“In this study we identified a common plasma microRNA profile in [Fabry disease] patients, useful not only for the correct classification of Fabry patients regardless of sex and age, but also to evaluate the response to therapy,” the researchers wrote.
“Furthermore, our observations suggest that some microRNAs of this profile demonstrate prognostic qualities,” they added.