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

Abstract

For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1-78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9-1340) ng/mL and 5.4 (1.5-16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9-1050), compared to GD1 and severe GBA1 variants, 447 (38-1340) ng/mL, and neuronopathic GD, 325 (116-1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5-15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5-16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7-10.7) in heterozygous GBA1 carriers with Parkinson's disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type.

• Authors: Tama Dinur, Peter Bauer, Christian Beetz, Guido Kramp, Claudia Cozma, Marius-Ionuț Iurașcu, Michal Becker-Cohen, Majdolen Istaiti, Arndt Rolfs, Ari Zimran, Shoshana Revel-Vilk
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 3 (Jan 30 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35163551 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Psychosine
• sphingosyl beta-glucoside
• GBA protein, human
• Glucosylceramidase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Child
• Child, Preschool
• Cross-Sectional Studies
• Early Detection of Cancer
• Female
• Gaucher Disease (blood, diagnosis, genetics)
• Glucosylceramidase (genetics)
• Humans
• Infant
• Male
• Middle Aged
• Mutation
• Psychosine (analogs & derivatives, blood)
• Young Adult