{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T02:01:42Z","timestamp":1776909702478,"version":"3.51.2"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"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), the deacylated form of glucocerebroside, was shown to be the most specific and sensitive biomarker for diagnosing Gaucher disease (GD). The aim of this study is to assess the contribution of lyso-Gb1 at the time of diagnosis for treatment decisions in na\u00efve patients with GD. Newly diagnosed patients from July 2014 to November 2022 were included in this retrospective cohort study. The diagnosis was done by sending a dry blood spot (DBS) sample for GBA1 molecular sequencing and lyso-Gb1 quantification. Treatment decisions were based on symptoms, signs, and routine laboratory tests. We diagnosed 97 patients (41 males), both type 1 (n = 87), and neuronopathic (n = 10). The median (range) age at diagnosis was 22 (1\u201378), with 36 children. In 65 patients, GD-specific therapy was started with a median (range) lyso-Gb1, 337 (60\u20131340) ng\/mL, significantly higher than in patients who did not go on to treatment, 153.5 (9\u2013442) ng\/mL. Using a receiver operating characteristic (ROC) analysis, a cutoff of lyso-Gb1 &gt; 250 ng\/mL was associated with treatment with a sensitivity of 71% and specificity of 87.5%. Predictors of treatment were thrombocytopenia, anemia, and elevated lyso-Gb1 (&gt;250 ng\/mL). In conclusion, lyso-Gb1 levels contribute to the medical decision related to the initiation of treatment, mainly among mildly affected newly diagnosed patients. For patients with a severe phenotype, as for all patients, the main value of lyso-Gb1 would be to monitor response to therapy. The variable methodology and differences in the units of lyso-Gb1 measurements between laboratories prevent the adaptation of the exact cut-off we found in general practice. However, the concept is that a significant elevation, i.e., a several-fold increase from the diagnostic lyso-Gb1 cutoff, is related to a more severe phenotype and, accordingly, to the decision regarding the initiation of GD-specific therapy.<\/jats:p>","DOI":"10.3390\/ijms24043945","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:04:03Z","timestamp":1676513043000},"page":"3945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Contribution of Glucosylsphingosine (Lyso-Gb1) to Treatment Decisions in Patients with Gaucher Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Tama","family":"Dinur","sequence":"first","affiliation":[{"name":"Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Bauer","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"}]},{"given":"Claudia","family":"Cozma","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Becker-Cohen","sequence":"additional","affiliation":[{"name":"Gaucher Unit, 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, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volha","family":"Skrahina","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"},{"name":"Arcensus GmbH, 18055 Rostock, Germany"}],"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, Shaare Zedek Medical Center, Jerusalem 9103102, 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, 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":[[2023,2,15]]},"reference":[{"key":"ref_1","unstructured":"Kaushansky, K., Lichtman, M., Prchal, J., Levi, M., Press, O., Burns, L., and Caligiuri, M. (2021). Williams Hematology, McGraw-Hill. [10th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/17446651.2018.1445524","article-title":"Recent advances in the diagnosis and management of Gaucher disease","volume":"13","author":"Gary","year":"2018","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/ajh.25701","article-title":"The road to biosimilars in rare diseases\u2014ongoing lessons from Gaucher disease","volume":"95","author":"Drelichman","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/bjh.15402","article-title":"How we manage Gaucher Disease in the era of choices","volume":"182","author":"Szer","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","article-title":"Elevated plasma glucosylsphingosine in Gaucher disease: Relation to phenotype, storage cell markers, and therapeutic response","volume":"118","author":"Dekker","year":"2011","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rolfs, A., Giese, A.K., Grittner, U., Mascher, D., Elstein, D., Zimran, A., Bottcher, T., Lukas, J., Hubner, R., and Golnitz, U. (2013). Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079732"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E140","DOI":"10.1002\/ajh.25074","article-title":"Glucosylsphingosine is a reliable response biomarker in Gaucher disease","volume":"93","author":"Arkadir","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/jimd.12192","article-title":"Expanding the clinical utility of glucosylsphingosine for Gaucher disease","volume":"43","author":"Saville","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1186\/s13023-022-02549-6","article-title":"An observational study to investigate the relationship between plasma glucosylsphingosine (lyso-Gb1) concentration and treatment outcomes of patients with Gaucher disease in Japan","volume":"17","author":"Ida","year":"2022","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dinur, T., Bauer, P., Beetz, C., Kramp, G., Cozma, C., Iurascu, M.I., Becker-Cohen, M., Istaiti, M., Rolfs, A., and Zimran, A. (2022). Gaucher Disease Diagnosis Using Lyso-Gb1 on Dry Blood Spot Samples: Time to Change the Paradigm?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031627"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4097\/kja.21209","article-title":"Receiver operating characteristic curve: Overview and practical use for clinicians","volume":"75","author":"Nahm","year":"2022","journal-title":"Korean J. Anesthesiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/17474086.2021.1908120","article-title":"Hematological manifestations and complications of Gaucher disease","volume":"14","author":"Szer","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1055\/a-1642-4206","article-title":"Platelet Activation and Reactivity in a Large Cohort of Patients with Gaucher Disease","volume":"122","author":"Naamad","year":"2022","journal-title":"Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3324\/haematol.2019.236083","article-title":"Accuracy of chitotriosidase activity and CCL18 concentration in assessing type I Gaucher disease severity. A systematic review with meta-analysis of individual participant data","volume":"106","author":"Raskovalova","year":"2021","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lukas, J., Cozma, C., Yang, F., Kramp, G., Meyer, A., Nesslauer, A.M., Eichler, S., Bottcher, T., Witt, M., and Brauer, A.U. (2017). Glucosylsphingosine Causes Hematological and Visceral Changes in Mice-Evidence for a Pathophysiological Role in Gaucher Disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102192"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cozma, C., Cullufi, P., Kramp, G., Hovakimyan, M., Velmishi, V., Gjikopulli, A., Tomori, S., Fischer, S., Oppermann, S., and Grittner, U. (2020). Treatment Efficiency in Gaucher Patients Can Reliably Be Monitored by Quantification of Lyso-Gb1 Concentrations in Dried Blood Spots. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134577"},{"key":"ref_17","unstructured":"(2023, February 10). Available online: https:\/\/www.ewggd.com\/ewggd-working-groups\/."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dinur, T., Zimran, A., Becker-Cohen, M., Arkadir, D., Cozma, C., Hovakimyan, M., Oppermann, S., Demuth, L., Rolfs, A., and Revel-Vilk, S. (2019). Long Term Follow-Up of 103 Untreated Adult Patients with Type 1 Gaucher Disease. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101662"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2022.03.001","article-title":"The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here?","volume":"136","author":"Weinreb","year":"2022","journal-title":"Mol. Genet Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hurvitz, N., Dinur, T., Becker-Cohen, M., Cozma, C., Hovakimyan, M., Oppermann, S., Demuth, L., Rolfs, A., Abramov, A., and Zimran, A. (2019). Glucosylsphingosine (lyso-Gb1) as a Biomarker for Monitoring Treated and Untreated Children with Gaucher Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123033"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Revel-Vilk, S., Fuller, M., and Zimran, A. (2020). Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197159"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1053\/j.semperi.2015.03.005","article-title":"Newborn screening for lysosomal storage disorders","volume":"39","author":"Matern","year":"2015","journal-title":"Semin. Perinatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s10545-017-0098-3","article-title":"Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy","volume":"41","author":"Burlina","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20180334","DOI":"10.1590\/1678-4685-gmb-2018-0334","article-title":"Newborn screening for lysosomal disorders in Brazil: A pilot study using customized fluorimetric assays","volume":"43","author":"Bender","year":"2020","journal-title":"Genet. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/jhg.2017.36","article-title":"Successful newborn screening for Gaucher disease using fluorometric assay in China","volume":"62","author":"Kang","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s10897-015-9879-8","article-title":"Newborn Screening for Lysosomal Storage Disorders: Views of Genetic Healthcare Providers","volume":"25","author":"Lisi","year":"2016","journal-title":"J. Genet. Couns."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1002\/jimd.12382","article-title":"Risk of postpartum hemorrhage in multiparous women with Gaucher disease: A call for reconsidering enzyme replacement therapy in all pregnant patients","volume":"44","author":"Cohen","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/qjmed\/91.7.483","article-title":"Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease","volume":"91","author":"Elstein","year":"1998","journal-title":"QJM"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/imj.15781","article-title":"Enzyme replacement therapy leading to improvement in myeloma indices in a patient with concomitant Gaucher disease","volume":"52","author":"Harel","year":"2022","journal-title":"Intern. Med. J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nguyen, Y., Stirnemann, J., Lautredoux, F., Cador, B., Bengherbia, M., Yousfi, K., Hamroun, D., Astudillo, L., Billette de Villemeur, T., and Brassier, A. (2020). Immunoglobulin Abnormalities in Gaucher Disease: An Analysis of 278 Patients Included in the French Gaucher Disease Registry. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041247"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.bcmd.2009.04.002","article-title":"Gaucher disease and monoclonal gammopathy: A report of 17 cases and impact of therapy","volume":"43","author":"Grosbois","year":"2009","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114402","DOI":"10.1016\/j.addr.2022.114402","article-title":"Lysosomal functions and dysfunctions: Molecular and cellular mechanisms underlying Gaucher disease and its association with Parkinson disease","volume":"187","author":"Horowitz","year":"2022","journal-title":"Adv. Drug Deliv. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3945\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:08Z","timestamp":1760121428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043945"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043945","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}