Addition of Lyso-Gb1 to enzyme activity to first-tier test for Gaucher in DBS improves diagnostic accuracy and reduces patient recall rate.

INTRODUCTION

The gold standard for diagnosing Gaucher disease (GD) is the detection of reduced beta-glucosidase (bGlu) activity in peripheral blood samples, in association with variant analysis of the GBA1 gene. Dried blood spot (DBS) specimens are accepted worldwide for first-tier testing of GD. Glucosylsphingosine (Lyso-Gb1) is considered an ideal disease biomarker. Our objective was to evaluate and describe our local experience in GD detection with an algorithm including determination of Lyso-Gb1 in DBS according to enzyme activity (EA) results.

METHODS

DBS data from patients with suspicion of GD were retrieved from electronic records. Lyso-Gb1 measurement and EA assay of bGlu and beta-galactosidase (bGal, control enzyme) were performed.

RESULTS

Data from 4651 patients were retrieved (50.82 % male; median age: 21 years [IQR: 4-50]). Median bGlu EA was 5.8 µmol/L/h (IQR: 4-8.6). Patients with normal bGlu EA (≥3µmol/L/h) were interpreted as negative for GD and excluded from further research. Lyso-Gb1 was quantified in DBS in 326 subjects with bGlu EA < 3µmol/L/h; in 46 samples (14.1 %), Lyso-Gb1 levels were above the cutoff value and considered for further confirmation of GD.

CONCLUSION

In our large cohort of patients with suspicion of GD and reduced bGlu EA, the determination of Lyso-Gb1 levels in DBS would lead to avoiding a second sample request in most cases. Simultaneous determination of bGlu activity and Lyso-Gb1 levels in DBS optimizes the diagnostic approach of individuals with suspicion of GD, independently of age and gender.