{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:00:04Z","timestamp":1791442804356,"version":"4.3.3"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016040","name":"Duke University Health Systems and an Investigator-Initiated Award from Shire Pharmaceuticals USA, a member of the Takeda group of companies","doi-asserted-by":"publisher","award":["IIR-USA 001544"],"award-info":[{"award-number":["IIR-USA 001544"]}],"id":[{"id":"10.13039\/100016040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and\/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients.<\/jats:p>","DOI":"10.3390\/ijms232314938","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T01:52:20Z","timestamp":1669773140000},"page":"14938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Matthew M.","family":"Gayed","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hye","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Huggins","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Rodriguez-Rassi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"DeArmey","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya Sunil","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee R.","family":"Stiles","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Biochemical Genetics Laboratory, Duke University Health System, Durham, NC 27713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"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. (2017). A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020441"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1615\/CritRevOncog.2013006060","article-title":"Gaucher disease: A comprehensive review","volume":"18","author":"Rosenbloom","year":"2013","journal-title":"Crit. Rev. Oncog."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Grabowski, G.A. (1993). Gaucher disease. Advances in Human Genetics 21, Springer.","DOI":"10.1007\/978-1-4615-3010-7_5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1172\/JCI117084","article-title":"Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease","volume":"93","author":"Hollak","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_5","unstructured":"Aerts, J.M., Boot, R.G., Renkema, G.H., Van Weely, S., Jones, S., Hollak, C.E., and van Oers, M. (1995). Molecular and biochemical abnormalities of Gaucher disease: Chitotriosidase, a newly identified biochemical marker. Seminars in Hematology, Elsevier."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/BF02436762","article-title":"Elevated plasma chitotriosidase activity in various lysosomal storage disorders","volume":"18","author":"Guo","year":"1995","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12931-019-1263-z","article-title":"Chitotriosidase: A biomarker of activity and severity in patients with sarcoidosis","volume":"21","author":"Bennett","year":"2020","journal-title":"Respir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25680","DOI":"10.1074\/jbc.273.40.25680","article-title":"The human chitotriosidase gene. Nature of inherited enzyme deficiency","volume":"273","author":"Boot","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.bcmd.2005.05.005","article-title":"Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease","volume":"35","author":"Deegan","year":"2005","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10545-014-9711-x","article-title":"Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy","volume":"37","author":"Hendriks","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rolfs, A., Giese, A.K., Grittner, U., Mascher, D., Elstein, D., Zimran, A., B\u00f6ttcher, T., Lukas, J., H\u00fcbner, R., and G\u00f6lnitz, 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_12","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.cbpa.2019.10.006","article-title":"Glycosphingolipids and lysosomal storage disorders as illustrated by gaucher disease","volume":"53","author":"Aerts","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/ajh.24491","article-title":"Glucosylsphingosine is a key biomarker of Gaucher disease","volume":"91","author":"Murugesan","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymgme.2017.08.005","article-title":"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","volume":"122","author":"Elstein","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","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_16","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_17","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_18","doi-asserted-by":"crossref","unstructured":"Dinur, T., Grittner, U., Revel-Vilk, S., Becker-Cohen, M., Istaiti, M., Cozma, C., Rolfs, A., and Zimran, A. (2021). 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., 22.","DOI":"10.3390\/ijms22147699"},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"100667","DOI":"10.1016\/j.ymgmr.2020.100667","article-title":"Patients with Gaucher disease display systemic oxidative stress dependent on therapy status","volume":"25","author":"Kartha","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13023-016-0413-3","article-title":"Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients","volume":"11","author":"Smid","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/ajh.25875","article-title":"Real-world effectiveness of eliglustat in treatment-na\u00efve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry","volume":"95","author":"Mistry","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/j.seminhematol.2004.07.010","article-title":"Gaucher disease type 1: Revised recommendations on evaluations and monitoring for adult patients","volume":"41","author":"Weinreb","year":"2004","journal-title":"Semin. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00431-012-1771-z","article-title":"Revised recommendations for the management of Gaucher disease in children","volume":"172","author":"Kaplan","year":"2013","journal-title":"Eur. J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jpeds.2003.10.067","article-title":"Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: Consensus recommendations","volume":"144","author":"Charrow","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00431-003-1363-z","article-title":"Paediatric non-neuronopathic Gaucher disease: Recommendations for treatment and monitoring","volume":"163","author":"Baldellou","year":"2004","journal-title":"Eur. J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cca.2020.10.007","article-title":"Combined analysis of plasma or serum glucosylsphingosine and globotriaosylsphingosine by UPLC-MS\/MS","volume":"511","author":"Beasley","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014A metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J. Biomed. Inform."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap consortium: Building an international community of software platform partners","volume":"95","author":"Harris","year":"2019","journal-title":"J. Biomed. Inform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bcmd.2009.09.006","article-title":"Force majeure: Therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease","volume":"44","author":"Hollak","year":"2010","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ymgmr.2017.06.003","article-title":"Treatment of profound thrombocytopenia in a patient with Gaucher disease type 1: Is there a role for substrate reduction therapy","volume":"12","author":"Ha","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/path.4452","article-title":"Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy","volume":"235","author":"Pavlova","year":"2015","journal-title":"J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/imj.14156","article-title":"Presenting signs and patient co-variables in Gaucher disease: Outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative","volume":"49","author":"Mehta","year":"2019","journal-title":"Intern. Med. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s40265-015-0468-9","article-title":"Eliglustat: A Review in Gaucher Disease Type 1","volume":"75","author":"Scott","year":"2015","journal-title":"Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ymgmr.2016.06.003","article-title":"Clinical response to eliglustat in treatment-na\u00efve patients with Gaucher disease type 1: Post-hoc comparison to imiglucerase-treated patients enrolled in the International Collaborative Gaucher Group Gaucher Registry","volume":"8","author":"Ibrahim","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ymgme.2015.05.012","article-title":"Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 na\u00efve to enzyme replacement therapy or previously treated with imiglucerase","volume":"117","author":"Smith","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/humu.20524","article-title":"Type 1 Gaucher disease: Null and hypomorphic novel chitotriosidase mutations-implications for diagnosis and therapeutic monitoring","volume":"28","author":"Grace","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cca.2007.02.042","article-title":"Monitoring of Gaucher patients with a novel chitotriosidase assay","volume":"381","author":"Schoonhoven","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ymgmr.2016.08.009","article-title":"Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial","volume":"9","author":"Pleat","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_42","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14938\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:29:10Z","timestamp":1760146150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14938"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":42,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314938"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314938","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]}}}