{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:51:33Z","timestamp":1776865893140,"version":"3.51.2"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"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>Glucosylsphingosine (lyso-Gb1) serves as a biomarker for evaluating disease activity in Gaucher disease (GD). While treatment-related changes are documented, the dynamics of lyso-Gb1 during untreated states remain poorly understood. This retrospective, longitudinal cohort study utilized a large GD database comprising 701 patients and over 6200 visits with lyso-Gb1 measurements. Patients with at least two untreated visits were included in the analysis (n = 272). A significant change was defined as \u226550 ng\/mL for lyso-Gb1, \u22651 g\/dL for hemoglobin, and \u226550 \u00d7 109\/L for platelet count. Multivariable logistic regression analyses identified clinical factors associated with lyso-Gb1 decline or an increase. During untreated states, 35 patients (12.9%; 95% CI 9.4\u201317.5%) exhibited a decline in lyso-Gb1, with a median decrease of 96.3 ng\/mL. This decline was more common in females (OR 3.50, p = 0.032) and associated with higher initial lyso-Gb1 levels (p &lt; 0.001) and baseline hemoglobin (p = 0.032). An increase in lyso-Gb1 was observed in 98 patients (36.0%; 95% CI 30.5\u201341.9%), with a median rise of 135.1 ng\/mL. This increase correlated with lower baseline platelet counts (p = 0.003), lower baseline hemoglobin (p = 0.002), and longer follow-up duration (p = 0.001). In many cases, lyso-Gb1 increases were observed without a preceding change in hemoglobin or platelet count. In summary, declines in lyso-Gb1 in untreated states are rare but possible. The association with female sex may reflect inflammatory effects. Although increases in lyso-Gb1 were expected without treatment, they occurred mainly in patients with higher disease severity markers. Nevertheless, most patients in the untreated states remained stable within \u00b150 ng\/mL. These findings demonstrate a heterogeneous trajectory of lyso-Gb1 across untreated states and highlight the importance of interpreting lyso-Gb1 changes within the clinical context when making treatment decisions.<\/jats:p>","DOI":"10.3390\/ijms27093726","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"3726","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucosylsphingosine (Lyso-Gb1) Dynamics in Untreated States in Gaucher Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Tama","family":"Dinur","sequence":"first","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9414-4555","authenticated-orcid":false,"given":"Peter","family":"Bauer","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-6944","authenticated-orcid":false,"given":"Sabine","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Kramp","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-6742","authenticated-orcid":false,"given":"Michal","family":"Becker-Cohen","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-2828","authenticated-orcid":false,"given":"Majdolen","family":"Istaiti","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3398-7584","authenticated-orcid":false,"given":"Dafna","family":"Frydman","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2088-0422","authenticated-orcid":false,"given":"Elena","family":"Shulman","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-8608","authenticated-orcid":false,"given":"Ari","family":"Zimran","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Agyany Pharma Ltd., Jerusalem 9695614, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-0337","authenticated-orcid":false,"given":"Shoshana","family":"Revel-Vilk","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., and Brassier, A. 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