Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?

Int J Mol Sci. 2022 Jan 30;23(3):1627. doi: 10.3390/ijms23031627.

PMID: 35163551

Tama Dinur, Peter Bauer, Christian Beetz

Highlights: A paradigm change may be considered for the diagnosis of Gaucher disease based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in dried blood spot.

Abstract

Background: Reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells, along with GBA1 mutation analysis, has been the gold standard for diagnosing Gaucher disease (GD) for years. Dried blood spot (DBS) specimens provide a number of advantages, including ease of collection, a minimal amount of blood required, and easier transportation. DBS, on the other hand, has limitations when it comes to assessing GCase activity.

Objective: This article describes a cross-sectional investigation and provide our seven-year experience diagnosing GD utilizing DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1).

Results: At a median (range) age of 21 (1-78) years, 99 (22.3%) of 444 examined patients were diagnosed with GD. Lyso-Gb levels were 252 (9-1340) ng/mL for genetically proven GD patients and 5.4 (1.5-16) ng/mL for participants without a GD diagnosis. GD1 and mild GBA1 variants exhibited lower median (range) lysoGb1, 194 (9-1050), than GD1 and severe GBA1 variants, 447 (38-1340), and neuronopathic GD, 325 (116- 1270) ng/mL (p = 0.001). When compared to wild-type GBA1 (4.9 (1.5-16), ng/mL)), subjects with heterozygous GBA1 variants (carrier) showed greater lyso-Gb1 levels, 5.8 (2.5-15.3) ng/mL (p = 0.001). LysoGb1 levels, median (range), were 5 (2.7-10.7) in heterozygous GBA1 carriers with Parkinson's disease (PD), similar to lyso-Gb1 levels in patients without PD.

Conclusion: A paradigm shift is proposed for diagnosing GD using lyso-Gb1 measures and confirming GBA1 mutation analyses in DBS. Lyso-Gb1 levels were not able to distinguish heterozygous GBA1 carriers from wild type.

Keywords: Gaucher, Gaucher disease, diagnosis, dry blood spot, glucosylsphingosine, lyso-Gb1