Looking at the activity of the Gaucher-associated enzyme — beta glucocerebrosidase (GBA) — using dried blood spot samples allows for an early diagnosis of likely Gaucher disease in children with mild or atypical symptoms, a study from China reports.
This finding could be particular importance to children at high risk for the disease but without easy access to centers able to give more definitive tests, and is a feasible preliminary screening method, the scientists said.
Gaucher is a rare genetic disease caused by mutations in the beta glucocerebrosidase (GBA) gene. Alterations to this gene result in a lack of enzyme activity, leading to a lipid (fat molecule) called glucocerebroside accumulating in cells of the spleen, liver, bone, lung, and brain.
Because this condition affects many organs and tissues, its signs and symptoms vary widely among affected individuals. The absence of specific symptoms and doctors’ poor understanding of this disease can delay diagnosis for several years — preventing early treatment.
Evidence shows enzyme replacement therapy reverses or eases many manifestations of Gaucher disease. However, its optimal effect is dependent on an early diagnosis.
Enzyme activity of beta glucosidase can be measured using a dry blood spot sample. Nonetheless, the gold standard for Gaucher diagnosis is a clear finding of poor beta glucosidase activity in white blood cells (leukocytes) and connective tissue cells (fibroblasts).
“A lot of [Gaucher disease] patients living far away from test centers cannot achieve definitive diagnosis until the typical symptoms and/or signs occur. These situations make most patients with [Gaucher disease] miss the best treatment time,” the researchers wrote.
A Gaucher’s diagnostic algorithm that focused on beta glucocerebrosidase activity in dried blood spots for screening was introduced in 2015 in China for patients with spleen and platelets problems.
The research team investigated the feasibility of this diagnostic algorithm by evaluating the dried blood spot approach in screening high-risk Gaucher disease children from the Shandong Province, and a study of Gaucher’s prevalence in this setting.
In total, 73 children (47 boys and 26 girls) with an enlarged spleen and/or low platelet levels were included in this study.
Eighteen had beta glucocerebrosidase activity lower than accepted boundary values. Of these 18, four patients ended up being diagnosed with Gaucher disease after molecular enzymatic analysis of their white blood cells.
Interestingly, researchers also found three mutations in the Gaucher’s gene that hadn’t been reported previously, which adds to the importance of this dried blood spot method in high-risk children.
In addition, “the prevalence of [Gaucher disease] in this selected population cohort of high risk children is 5.5%,” the scientists noted.
“This algorithm was proved to be appropriate to make an early diagnosis of [Gaucher disease] patients with mild symptoms or atypical symptoms and avoid diagnosis delay. DBS [dried blood spot] method is convenient for preparation, storage and transport, and can effectively screen out [Gaucher] patients, which can be used as a preliminary screening method for diagnosis,” the team concluded.
The work was led by researchers at the Pediatric Center, Affiliated Hospital of Qingdao University in Qingdao, and the Department of Pediatrics, Shengli Oilfield Central Hospital in Dongying, China.