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.
Highlights
Gaucher disease (GD), one of the most common lysosomal storage disorders, is caused by a mutant lysosomal enzyme β-glucocerebrosidase (GCase), leading to the storage of glucocerebroside (GC) and other glycolipids in various tissues; it leads to a multi-system disease known for its great phenotypic heterogeneity [1,2]
The current gold standard for diagnosing GD is the detection of reduced GCase activity in peripheral blood cells, combined with mutation analysis at the DNA level of the glucocerebrosidase gene (GBA1), performed today by whole-gene sequence [1]
dried blood spot (DBS) samples were sent for GBA1 molecular sequencing and lyso-Gb1 quantification
Summary
Gaucher disease (GD), one of the most common lysosomal storage disorders, is caused by a mutant lysosomal enzyme β-glucocerebrosidase (GCase), leading to the storage of glucocerebroside (GC) and other glycolipids in various tissues; it leads to a multi-system disease known for its great phenotypic heterogeneity [1,2]. The current gold standard for diagnosing GD is the detection of reduced GCase activity in peripheral blood cells (traditionally compared to same-day normal controls), combined with mutation analysis at the DNA level of the glucocerebrosidase gene (GBA1), performed today by whole-gene sequence [1]. Bone-marrow aspiration and biopsies for identifying Gaucher cells are no longer acceptable as a means to diagnose GD and should be performed only when another hematologic comorbidity is being evaluated [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
