Elevated uric acid levels linked to disease severity in type 1 Gaucher
Study finds trait could be useful in diagnosing, monitoring of patients
High levels of uric acid may be a biomarker of disease severity in people with type 1 Gaucher disease, the most common form of the disorder, according to a new study.
Researchers found that patients with more severe disease had significantly higher levels of uric acid in their blood compared with those who had milder disease. Uric acid is a waste product formed during the metabolism of purines, components of the building blocks of DNA and RNA.
“As the test for [blood uric acid] is readily available and reliable, our study highly suggests that [blood uric acid] levels should be included in the [Gaucher disease] biomarker ‘basket’ for the diagnosis and monitoring of patients,” researchers wrote.
The study, “Hyperuricaemia in type 1 Gaucher disease: is uric acid a biomarker for disease severity?,” was published in the Internal Medicine Journal.
Biomarkers routinely used to support diagnosis
Gaucher disease is caused by mutations in the GBA1 gene, which lead to a deficiency in an enzyme that’s needed for breaking down a fatty molecule called glucocerebroside (Gb1). Without this enzyme, Gb1 builds up inside immune cells — particularly macrophages — which become chronically activated and accumulate in various organs, leading to inflammation, organ damage, and Gaucher disease symptoms.
While disease severity is typically assessed based on the extent of organ involvement, several Gaucher-specific biomarkers — molecules that reflect disease activity — are routinely used to support diagnosis, monitor disease progression, and evaluate responses to treatment.
Recently, elevated blood uric acid levels were described for the first time in individuals with type 1 Gaucher disease. As uric acid has been shown in other conditions to rise alongside ferritin, a common biomarker of disease severity in Gaucher disease, this raised the possibility of a link between elevated uric acid levels, or hyperuricemia, and Gaucher disease activity.
To examine this link, a group of researchers in Israel set out to explore how common hyperuricemia is in type 1 Gaucher disease, whether it is associated with disease severity, and if it might be linked to an increased risk of cancer or blood-related conditions commonly seen in Gaucher disease.
The team analyzed data from 69 adults who had been followed at the Gaucher Clinic at Rambam Health Care Campus in Haifa, Israel, since 1990. Among those patients, 25 had never received treatment and 44 were on enzyme replacement therapy (ERT), a standard Gaucher treatment.
Disease severity was assessed using the Zimran Severity Score Index (SSI), which evaluates organ enlargement, blood counts, bone involvement, and other clinical features of Gaucher disease. On average, the SSI across all patients was nearly 9. Those receiving ERT had more advanced disease, with an average SSI of 11.6, compared with 4.48 in untreated individuals.
Elevated blood uric acid levels more likely in patients with severe Gaucher
Overall, the researchers found a statistically significant correlation between uric acid levels and disease severity, indicating that higher blood uric acid levels were more likely to occur in individuals with more severe Gaucher disease.
A significant association was also observed between uric acid levels and acid phosphatase, a known biomarker of macrophage activation and inflammation whose levels are typically linked to Gaucher disease severity. No significant association was found between uric acid and ferritin levels.
To assess whether uric acid levels change with treatment, blood uric acid levels was measured in 30 patients before starting ERT and again after two years. Results showed a statistically significant increase in levels, particularly in men.
Hence, we hypothesise that [blood uric acid] reflects the proinflammatory state of [type 1 Gaucher disease], which enables prediction of the disease course related to the severity and development of complications.
The researchers suggested this rise, even after treatment, might reflect increased purine metabolism resulting from macrophage activation and persistent inflammation that ERT cannot fully address.
“Hence, we hypothesise that [blood uric acid] reflects the proinflammatory state of [type 1 Gaucher disease], which enables prediction of the disease course related to the severity and development of complications,” the researchers wrote.
No significant association was found between blood uric acid levels and cancer or blood-related conditions.
“Biomarkers are helpful in the diagnosis and follow-up of [Gaucher disease] patients,” the researchers wrote.
Given the growing recognition of glucosylsphingosine (Lyso-Gb1) — a modified fatty molecule derived from the breakdown of Gb1 — as a highly specific and sensitive biomarker for Gaucher disease, the researchers concluded that it would “be essential to evaluate the correlation between [blood uric acid] and Lyso-Gb1 in the future.”
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