{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:49:22Z","timestamp":1787507362780,"version":"build-2736575974"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Gaucher Outcome Survey is sponsored by Takeda Pharmaceutical Company Limited","award":["The Gaucher Outcome Survey is sponsored by Takeda Pharmaceutical Company Limited"],"award-info":[{"award-number":["The Gaucher Outcome Survey is sponsored by Takeda Pharmaceutical Company Limited"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with Gaucher disease (GD) require continual monitoring; however, lack of specific disease biomarkers was a significant challenge in the past. Glucosylsphingosine (lyso-Gb1) has been shown to be a reliable, key, specific, and sensitive biomarker for diagnosis, prognosis, and treatment response in clinical studies of patients with GD. We evaluated the change in lyso-Gb1 concentration over time following enzyme replacement therapy in patients with confirmed GD using real-world data from the Gaucher Outcome Survey disease registry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data for patients aged\u2009\u2265\u200918 years with a confirmed diagnosis of GD and at least two lyso-Gb1 assessments were analyzed retrospectively. Patients were stratified by treatment status at baseline (time of first lyso-Gb1 assessment). Lyso-Gb1 concentrations were measured from dried blood spot (DBS) samples by Centogene AG. Assessments included change in lyso-Gb1 concentration, hemoglobin concentration, platelet counts, and spleen and liver volume from baseline to the last lyso-Gb1 assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 2007 patients enrolled in the Gaucher Outcome Survey as of February 25, 2022, 435 met the inclusion criteria and were included in the study: 318 treated (\u2018all treated\u2019; 277 receiving treatment at baseline, 41 treatment naive at baseline), 38 receiving treatment at baseline who stopped treatment before the last lyso-Gb1 assessment, and 79 untreated. Lyso-Gb1 concentrations decreased from baseline to the last lyso-Gb1 assessment for all treated patients (median change \u2212\u20098.6\u00a0ng\/mL), and increased for untreated patients (median change 25.0\u00a0ng\/mL) and those who stopped treatment (median change 19.5\u00a0ng\/mL). Decreases were greater for all treatment-naive than previously treated patients (median change \u2212\u2009120.5 vs. \u2212\u20093.3\u00a0ng\/mL) and for velaglucerase alfa\u2013treated patients vs. the overall treated cohort (\u201332.6 vs. \u2212\u20098.6\u00a0ng\/mL). Small improvements in hemoglobin concentrations, platelet counts, and spleen volume were observed for treated patients but not untreated\/stopped treatment cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, changes in lyso-Gb1 concentrations from DBS were reflective of responses to enzyme replacement therapy initiation or withdrawal in most patients. These findings confirm that the use of DBS samples for routine monitoring of lyso-Gb1 concentrations in patients with GD is feasible in real-world settings and may be useful to assess treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-024-03444-y","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T04:39:27Z","timestamp":1738125567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey"],"prefix":"10.1186","volume":"20","author":[{"given":"Ari","family":"Zimran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoshana","family":"Revel-Vilk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tama","family":"Dinur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majdolen","family":"Istaiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaco","family":"Botha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Lukina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Giraldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Deegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan vom","family":"Dahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"3444_CR1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.cbpa.2019.10.006","volume":"53","author":"J Aerts","year":"2019","unstructured":"Aerts J, Kuo CL, Lelieveld LT, et al. Glycosphingolipids and lysosomal storage disorders as illustrated by Gaucher disease. Curr Opin Chem Biol. 2019;53:204\u201315.","journal-title":"Curr Opin Chem Biol"},{"key":"3444_CR2","doi-asserted-by":"crossref","unstructured":"Ferraz MJ, Kallemeijn WW, Mirzaian M, et al. Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses. Biochim Biophys Acta. 2014;1841(5):811\u201325.","DOI":"10.1016\/j.bbalip.2013.11.004"},{"issue":"5","key":"3444_CR3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/humu.20676","volume":"29","author":"KS Hruska","year":"2008","unstructured":"Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008;29(5):567\u201383.","journal-title":"Hum Mutat"},{"key":"3444_CR4","volume-title":"Williams hematology","author":"A Zimran","year":"2016","unstructured":"Zimran A, Elstein D. Gaucher disease and related lysosomal storage diseases. In: Kaushanksy K, Lichtman M, Prchal J, Levi MM, Press O, Burns L, Caligiuri M, editors. Williams hematology. 9th ed. New York, NY, USA: McGraw-Hill; 2016.","edition":"9"},{"issue":"4","key":"3444_CR5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1097\/MPH.0000000000002506","volume":"45","author":"M Wang","year":"2023","unstructured":"Wang M, Li F, Zhang J, Lu C, Kong W. Global epidemiology of Gaucher disease: an updated systematic review and meta-analysis. J Pediatr Hematol Oncol. 2023;45(4):181\u20138.","journal-title":"J Pediatr Hematol Oncol"},{"issue":"3","key":"3444_CR6","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.3390\/ijms23031627","volume":"23","author":"T Dinur","year":"2022","unstructured":"Dinur T, Bauer P, Beetz C, et al. Gaucher disease diagnosis using lyso-Gb1 on dry blood spot samples: time to change the paradigm? Int J Mol Sci. 2022;23(3):1627.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"3444_CR7","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3390\/ijns6020026","volume":"6","author":"SJ Moat","year":"2020","unstructured":"Moat SJ, George RS, Carling RS. Use of dried blood spot specimens to monitor patients with inherited metabolic disorders. Int J Neonatal Screen. 2020;6(2):26.","journal-title":"Int J Neonatal Screen"},{"issue":"13","key":"3444_CR8","doi-asserted-by":"publisher","first-page":"4577","DOI":"10.3390\/ijms21134577","volume":"21","author":"C Cozma","year":"2020","unstructured":"Cozma C, Cullufi P, Kramp G, et al. Treatment efficiency in Gaucher patients can reliably be monitored by quantification of lyso-Gb1 concentrations in dried blood spots. Int J Mol Sci. 2020;21(13):4577.","journal-title":"Int J Mol Sci"},{"key":"3444_CR9","doi-asserted-by":"crossref","unstructured":"Dinur T, Bauer P, Beetz C, et al. Contribution of glucosylsphingosine (lyso-Gb1) to treatment decisions in patients with gaucher disease. Int J Mol Sci. 2023;24(4):3945.","DOI":"10.3390\/ijms24043945"},{"issue":"3","key":"3444_CR10","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1002\/jimd.12192","volume":"43","author":"JT Saville","year":"2020","unstructured":"Saville JT, McDermott BK, Chin SJ, Fletcher JM, Fuller M. Expanding the clinical utility of glucosylsphingosine for Gaucher disease. J Inherit Metab Dis. 2020;43(3):558\u201363.","journal-title":"J Inherit Metab Dis"},{"issue":"16","key":"3444_CR11","doi-asserted-by":"publisher","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","volume":"118","author":"N Dekker","year":"2011","unstructured":"Dekker N, van Dussen L, Hollak CE, et al. Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood. 2011;118(16):e118\u201327.","journal-title":"Blood"},{"key":"3444_CR12","doi-asserted-by":"crossref","unstructured":"Rolfs A, Giese AK, Grittner U, et al. 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. 2013;8(11):e79732.","DOI":"10.1371\/journal.pone.0079732"},{"key":"3444_CR13","first-page":"17","volume":"13","author":"F Curado","year":"2023","unstructured":"Curado F, Rosner S, Zielke S, et al. Insights into the value of Lyso-Gb1 as a predictive biomarker in treatment-naive patients with Gaucher Disease Type 1 in the LYSO-PROOF study. Diagnostics (Basel). 2023;13:17.","journal-title":"Diagnostics (Basel)"},{"issue":"6","key":"3444_CR14","doi-asserted-by":"publisher","first-page":"E140","DOI":"10.1002\/ajh.25074","volume":"93","author":"D Arkadir","year":"2018","unstructured":"Arkadir D, Dinur T, Revel-Vilk S, et al. Glucosylsphingosine is a reliable response biomarker in Gaucher disease. Am J Hematol. 2018;93(6):E140\u20132.","journal-title":"Am J Hematol"},{"key":"3444_CR15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/ijms241914440","volume":"24","author":"V Malinova","year":"2023","unstructured":"Malinova V, Poupetova H, Reboun M, et al. Long-term evaluation of biomarkers in the Czech Cohort of Gaucher patients. Int J Mol Sci. 2023;24:19.","journal-title":"Int J Mol Sci"},{"key":"3444_CR16","doi-asserted-by":"crossref","unstructured":"Elstein D, Mellgard B, Dinh Q, et al. Reductions in glucosylsphingosine (lyso-Gb1) in treatment-na\u00efve and previously treated patients receiving velaglucerase alfa for type 1 Gaucher disease: data from phase 3 clinical trials. Mol Genet Metab. 2017;122(1\u20132):113\u201320.","DOI":"10.1016\/j.ymgme.2017.08.005"},{"issue":"2","key":"3444_CR17","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.neulet.2009.12.007","volume":"469","author":"XY Mao","year":"2010","unstructured":"Mao XY, Burgunder JM, Zhang ZJ, et al. Association between GBA L444P mutation and sporadic Parkinson\u2019s disease from Mainland China. Neurosci Lett. 2010;469(2):256\u20139.","journal-title":"Neurosci Lett"},{"issue":"19","key":"3444_CR18","doi-asserted-by":"publisher","first-page":"7159","DOI":"10.3390\/ijms21197159","volume":"21","author":"S Revel-Vilk","year":"2020","unstructured":"Revel-Vilk S, Fuller M, Zimran A. Value of glucosylsphingosine (lyso-Gb1) as a biomarker in Gaucher disease: a systematic literature review. Int J Mol Sci. 2020;21(19):7159.","journal-title":"Int J Mol Sci"},{"key":"3444_CR19","doi-asserted-by":"crossref","unstructured":"Mirzaian M, Wisse P, Ferraz MJ, et al. Mass spectrometric quantification of glucosylsphingosine in plasma and urine of type 1 Gaucher patients using an isotope standard. Blood Cells Mol Dis. 2015;54(4):307\u201314.","DOI":"10.1016\/j.bcmd.2015.01.006"},{"issue":"11","key":"3444_CR20","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1002\/ajh.24491","volume":"91","author":"V Murugesan","year":"2016","unstructured":"Murugesan V, Chuang WL, Liu J, et al. Glucosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol. 2016;91(11):1082\u20139.","journal-title":"Am J Hematol"},{"issue":"9","key":"3444_CR21","doi-asserted-by":"publisher","first-page":"E561","DOI":"10.1002\/ajh.24816","volume":"92","author":"M Franco","year":"2017","unstructured":"Franco M, Reihani N, Marin M, et al. Effect of velaglucerase alfa enzyme replacement therapy on red blood cell properties in Gaucher disease. Am J Hematol. 2017;92(9):E561\u20133.","journal-title":"Am J Hematol"},{"issue":"6","key":"3444_CR22","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/1873-3468.12104","volume":"590","author":"MJ Ferraz","year":"2016","unstructured":"Ferraz MJ, Marques AR, Appelman MD, et al. Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases. FEBS Lett. 2016;590(6):716\u201325.","journal-title":"FEBS Lett"},{"key":"3444_CR23","doi-asserted-by":"crossref","unstructured":"Ben Turkia H, Gonzalez DE, Barton NW, et al. Velaglucerase alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease. Am J Hematol. 2013;88(3):179\u201384.","DOI":"10.1002\/ajh.23382"},{"issue":"3","key":"3444_CR24","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1002\/ajh.23381","volume":"88","author":"DE Gonzalez","year":"2013","unstructured":"Gonzalez DE, Turkia HB, Lukina EA, et al. Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: results from a randomized, double-blind, multinational, phase 3 study. Am J Hematol. 2013;88(3):166\u201371.","journal-title":"Am J Hematol"},{"key":"3444_CR25","doi-asserted-by":"crossref","unstructured":"Zimran A, Altarescu G, Philips M, et al. Phase 1\/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. 2010;115(23):4651\u20136.","DOI":"10.1182\/blood-2010-02-268649"},{"issue":"3","key":"3444_CR26","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/ajh.23383","volume":"88","author":"A Zimran","year":"2013","unstructured":"Zimran A, Pastores GM, Tylki-Szymanska A, et al. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol. 2013;88(3):172\u20138.","journal-title":"Am J Hematol"},{"key":"3444_CR27","doi-asserted-by":"crossref","unstructured":"Zimran A, Belmatoug N, Bembi B, et al. Demographics and patient characteristics of 1209 patients with Gaucher disease: descriptive analysis from the Gaucher Outcome Survey (GOS). Am J Hematol. 2018;93(2):205\u201312.","DOI":"10.1002\/ajh.24957"},{"key":"3444_CR28","doi-asserted-by":"crossref","unstructured":"Hurvitz N, Dinur T, Becker-Cohen M, et al. Glucosylsphingosine (lyso-Gb1) as a biomarker for monitoring treated and untreated children with Gaucher disease. Int J Mol Sci. 2019;20(12):3033.","DOI":"10.3390\/ijms20123033"},{"issue":"14","key":"3444_CR29","doi-asserted-by":"publisher","first-page":"7699","DOI":"10.3390\/ijms22147699","volume":"22","author":"T Dinur","year":"2021","unstructured":"Dinur T, Grittner U, Revel-Vilk S, et al. Impact of long-term enzyme replacement therapy on glucosylsphingosine (lyso-Gb1) values in patients with type 1 Gaucher disease: statistical models for comparing three enzymatic formulations. Int J Mol Sci. 2021;22(14):7699.","journal-title":"Int J Mol Sci"},{"key":"3444_CR30","doi-asserted-by":"crossref","unstructured":"Elstein D, Altarescu G, Maayan H, et al. Booster-effect with velaglucerase alfa in patients with Gaucher disease switched from long-term imiglucerase therapy: early access program results from Jerusalem. Blood Cells Mol Dis. 2012;48(1):45\u201350.","DOI":"10.1016\/j.bcmd.2011.09.009"},{"issue":"4","key":"3444_CR31","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1111\/bjh.15402","volume":"182","author":"S Revel-Vilk","year":"2018","unstructured":"Revel-Vilk S, Szer J, Mehta A, Zimran A. How we manage Gaucher disease in the era of choices. Br J Haematol. 2018;182(4):467\u201380.","journal-title":"Br J Haematol"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03444-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03444-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03444-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T04:39:35Z","timestamp":1738125575000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03444-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3444"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03444-y","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]},"assertion":[{"value":"19 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The GOS was approved by the ethics institutional review boards of the participating centers. Furthermore, this registry was compliant with relevant global and local regulations and best practices: Good Pharmacoepidemiological Practice and Good Research for Comparative Effectiveness principles. The relevant principles of the International Council for Harmonisation Good Clinical Practice guidelines (ICH E6) were followed as appropriate for an observational registry, consistent with the Declaration of Helsinki. All participants gave written informed consent. ClinicalTrials.gov, NCT03291223.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AZ has received honoraria from BioEvents, Pfizer, and Takeda, and has received consultancy fees from Insightec, NLC Pharma, Prevail Therapeutics, and Takeda. SR-V has received research grants, speaker fees, and travel support from Pfizer, Sanofi Genzyme, and Takeda. JB is an employee of Takeda Pharmaceuticals International AG, Zurich, Switzerland and a stockholder of Takeda Pharmaceuticals Company, Limited. PG has received financial compensation for presentations, advisory boards, and research projects from Pfizer, Sanofi Genzyme, and Takeda. The financial contributions are destined to research in Gaucher disease and other lysosomal diseases through the FEETEG. PD has received speaker honoraria and institutional research support from Sanofi and Takeda. SvD has received compensation for presentations, advisory boards, and research projects from Pfizer, Sanofi Genzyme, and Takeda Shire. TD and MI declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}