The test proved useful in diagnosing newborns and was also accurate in placenta samples, suggesting that it could help diagnose the disease during pregnancy.
The study, “Expanding the clinical utility of glucosylsphingosine for Gaucher disease,” was published in the Journal of Inherited Metabolic Disease.
GD is caused by mutations in the GBA1 gene, which contains instructions to produce the enzyme beta-glucocerebrosidase. This enzyme breaks down a type of lipid (fat) called glucosylceramide. In people with GD, beta-glucocerebrosidase is formed incorrectly, leading to the buildup of glucosylceramide and its by-product glucosylsphingosine in cells.
Studies have shown that glucosylsphingosine is a specific biomarker of GD that helps diagnose the disease before the onset of symptoms, assess its activity and progression, and monitor response to treatment.
Researchers in Australia developed a rapid assay that measures glucosylsphingosine levels using dried filter paper blood spots (DBS), in which blood samples are applied and dried on filter paper.
“The simplicity of measurement in DBS coupled with the stability of [glucosylsphingosine] in this matrix … and ease of collection suggests this could be an alternative to [beta-glucocerebrosidase] measurements for high throughput screening,” the researchers wrote.
They also assessed whether the test could help differentiate people with GD from non-affected individuals and if there were noticeable differences in glucosylsphingosine levels among people with different types of GD.
Results showed that people with GD had significantly higher glucosylsphingosine levels in the blood than people without any metabolic disease or with a metabolic disease other than GD. The test correctly differentiated 23 people who had been clinically and genetically diagnosed with GD from 100 controls.
GD patients with neurological symptoms (median age of 6 months) had significantly higher levels of glucosylsphingosine than those without such symptoms (46 years; typically type 1), suggesting the possibility of differentiating disease type.
Also, the test correctly diagnosed a one-day-old baby who was suspected of having GD because his brother had the disorder. The researchers also tested 18 placental samples — 10 from babies who were later diagnosed with GD and eight from controls. The test showed significant differences between the two groups.
Taken together, these results suggest that elevated levels of glucosylsphingosine start early in life and that the biomarker could be used to diagnose GD in newborns and during pregnancy.
“[W]e provide data to extend the applicability of [glucosylsphingosine] determinations in screening programs and in the prenatal setting,” the researchers said. “Measurement of [glucosylsphingosine] is easy and reliable, and inevitably is proving to be a valuable diagnostic biomarker for GD.”
Since 2015, the investigators correctly identified 20 GD cases by measuring glucosylsphingosine in the blood.