Testing dried blood spots is an easy, inexpensive, and effective way for the early diagnosis of Gaucher disease (GD) types 2 and 3 in high-risk patients, according to researchers from Japan.
The research, “High-risk screening for Gaucher disease in patients with neurological symptoms,” appeared in the Journal of Human Genetics.
Gaucher disease is traditionally classified into three subtypes based on the absence (type 1) or presence — types 2 and 3, collectively called neuronopathic — of neurological symptoms. Although type 1 GD is the most common disease type in Europe and the U.S., the neurological subtypes are the most prevalent in Japan.
As Gaucher disease is rare and disease symptoms may be complex, patients are often misdiagnosed or remain undiagnosed. Screening people at high-risk and exhibiting neurological symptoms could improve Gaucher diagnosis and treatment.
Current screening for Gaucher is performed by measuring the activity of glucocerebrosidase (GCase), the enzyme that is deficient in these patients, from blood samples.
But evaluating dried blood spot samples could provide easy, inexpensive, and more efficient screening, and offer practical collection and storing. These features are especially valuable for populations with limited access to expensive equipment, researchers said.
The scientists included 102 people (55 males, ages 0-57, mean age 10.5) with diverse neurological symptoms, including seizures, involuntary movements, and oculomotor impairments.
Participants were tested with a dried blood spot-based assay to measure GCase activity. This approach detected two patients with very low enzyme activity. After a subsequent analysis of the GBA gene, which provides instructions to make GCase and is mutated in Gaucher patients, these two people were diagnosed with the disease.
Both exhibited prominent features of Gaucher, such as abnormal eye movements and enlarged liver and/or spleen. Only 8% of the total 102 participants had either manifestation, but not both. Some participants also had a low platelet count — an additional Gaucher-related abnormality — but were not diagnosed with the disease.
The GBA mutation found in patient 1 had already been described in type 2 Gaucher patients. And one of the two mutations found in patient 2 had not been reported in prior studies.
Findings in patient 1 led to a diagnosis of perinatal-lethal-type Gaucher disease. Although this type has limited treatment possibilities, the importance of patient counseling was emphasized.
In patient 2, early diagnosis enabled clinicians to begin enzyme replacement therapy (ERT), which markedly improved the infant’s blood condition and general health.
“This simple screening protocol using DBS [dried blood spot] samples is useful for early diagnosis of GD in high-risk and underdiagnosed patients suffering from various neurological symptoms,” the researchers wrote.