High-risk screening for Gaucher disease in patients with neurological symptoms

Abstract

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the deficiency of glucocerebrosidase enzyme activity. Clinical phenotypes of GD are categorized into three groups: (i) non-neuronopathic GD (type 1), (ii) acute neuronopathic GD (type 2) and (iii) subacute neuronopathic GD (type 3). The high-risk screening of neuronopathic GD has been performed using an enzymatic assay on the dried blood spot (DBS) samples. We enrolled a total of 102 individuals (47 females, 55 males; 0-57 years old; median age 10.5 years) with various neurological symptoms. We detected two patients with very low enzyme activity and they were diagnosed with the disease by using glucocerebrosidase gene analysis. Patient 1 was found to be compound heterozygous for the p.R159W/p.R170C locus and patient 2 was found to harbor two mutations at the IVS7+1G>T (c.999+1G>T) and p.L483P sites. This simple screening protocol using DBS samples is useful for early diagnosis of GD in high-risk and underdiagnosed patients suffering from various neurological symptoms.

Screening for Gaucher Disease Using Dried Blood Spot Tests: A Japanese Multicenter, Cross-sectional Survey

“…In the current analysis, after measuring the GBA activity in the 994 enrolled patients using the simplified DBS method, the number of patients with a low GBA activity was determined to be 12 (1.2%). This proportion of affected patients is in line with data reported from a previous study using a very similar test to screen for GD with neurological symptoms in high-risk Japanese patients (N=102, aged 0 to 57 years), in which 2 patients (2.0%) were found to have a low GBA activity (26). The utility of the first-tier DBS screen in that study was subsequently confirmed by genetic testing, by which both patients with low activity were found to have GD-related mutations (26).…”

“…This proportion of affected patients is in line with data reported from a previous study using a very similar test to screen for GD with neurological symptoms in high-risk Japanese patients (N=102, aged 0 to 57 years), in which 2 patients (2.0%) were found to have a low GBA activity (26). The utility of the first-tier DBS screen in that study was subsequently confirmed by genetic testing, by which both patients with low activity were found to have GD-related mutations (26). Similarly, a recent Chi-nese pilot analysis evaluated the utility of a DBS test for GBA activity in children (18 days to 14 years old) at a high risk of GD (35).…”

“…The screening protocol for GBA was performed on DBS samples using the method described previously (26), with minor modification. In brief, the study investigator collected blood samples (approximately 1 mL) from each registered patient and spotted it onto a piece of filter paper.…”

“…A simplified method for screening newborn babies using dried blood spots (DBS) on filter paper has recently been developed (26). In this simplified assay, the GBA activity can be easily measured by mailing the filter paper that has absorbed the blood to a specialized laboratory.…”

“…In this simplified assay, the GBA activity can be easily measured by mailing the filter paper that has absorbed the blood to a specialized laboratory. This method allows for the easy storage of the sample, so ordering the assay from a distance is feasible (26). In addition, this assay only requires 1 mL of blood, which means that it is relatively non-invasive and decreases the patient burden.…”