{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:50:19Z","timestamp":1792263019018,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced \u03b2-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\u201378) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9\u20131340) ng\/mL and 5.4 (1.5\u201316) ng\/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9\u20131050), compared to GD1 and severe GBA1 variants, 447 (38\u20131340) ng\/mL, and neuronopathic GD, 325 (116\u20131270) ng\/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5\u201315.3) ng\/mL, compared to wild-type GBA1, 4.9 (1.5\u201316), ng\/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7\u201310.7) in heterozygous GBA1 carriers with Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms23031627","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"1627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?"],"prefix":"10.3390","volume":"23","author":[{"given":"Tama","family":"Dinur","sequence":"first","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7061-2895","authenticated-orcid":false,"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Kramp","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cozma","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius-Ionu\u021b","family":"Iura\u0219cu","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Becker-Cohen","sequence":"additional","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-2828","authenticated-orcid":false,"given":"Majdolen","family":"Istaiti","sequence":"additional","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"},{"name":"Medical Faculty, University of Rostock, 18051 Rostock, Germany"},{"name":"Arcensus GmbH, 18055 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-8608","authenticated-orcid":false,"given":"Ari","family":"Zimran","sequence":"additional","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-0337","authenticated-orcid":false,"given":"Shoshana","family":"Revel-Vilk","sequence":"additional","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"ref_1","unstructured":"Kaushansky, K., Lichtman, M., Prchal, J., Levi, M., Press, O., Burns, L., and Caligiuri, M. 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