{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:30:31Z","timestamp":1775032231152,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["1R01HD102545-01A1"],"award-info":[{"award-number":["1R01HD102545-01A1"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HD065767"],"award-info":[{"award-number":["1R01HD065767"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30GM114736"],"award-info":[{"award-number":["P30GM114736"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Glycosaminoglycans (GAGs) are present in proteoglycans, which play critical physiological roles in various tissues. They are known to be elevated in mucopolysaccharidoses (MPS), a group of rare inherited metabolic diseases in which the lysosomal enzyme required to break down one or more GAG is deficient. In a previous study, we found elevation of GAGs in a subset of patients without MPS. In the current study, we aim to investigate serum GAG levels in patients with conditions beyond MPS. In our investigated samples, the largest group of patients had a clinical diagnosis of viral or non-viral encephalopathy. Clinical diagnoses and conditions also included epilepsy, fatty acid metabolism disorders, respiratory and renal disorders, liver disorders, hypoglycemia, developmental disorders, hyperCKemia, myopathy, acidosis, and vomiting disorders. While there was no conclusive evidence across all ages for any disease, serum GAG levels were elevated in patients with encephalopathy and some patients with other conditions. These preliminary findings suggest that serum GAGs are potential biomarkers in MPS and other disorders. In conclusion, we propose that GAGs elevated in blood can be used as biomarkers in the diagnosis and prognosis of various diseases in childhood; however, further designed experiments with larger sample sizes are required.<\/jats:p>","DOI":"10.3390\/diagnostics11091563","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Glycosaminoglycans as Biomarkers for Mucopolysaccharidoses and Other Disorders"],"prefix":"10.3390","volume":"11","author":[{"given":"Paige","family":"Amendum","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaukat","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shimane University, Izumo 693-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shimane University, Izumo 693-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Ago","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-2834","authenticated-orcid":false,"given":"Yasuyuki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Medical Education Development Center, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-8076","authenticated-orcid":false,"given":"Betul","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estera","family":"Rintz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-6605","authenticated-orcid":false,"given":"Jobayer","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA"},{"name":"Department of Biomedical Research, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Shimane University, Izumo 693-8501, Japan"},{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1016\/j.bbagen.2017.06.010","article-title":"Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan","volume":"1861","author":"Miyata","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/glycob\/cwy003","article-title":"Keratan sulfate, a complex glycosaminoglycan with unique functional capability","volume":"28","author":"Caterson","year":"2018","journal-title":"Glycobiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00418-008-0485-9","article-title":"Extracellular matrix of the central nervous system: From neglect to challenge","volume":"130","author":"Zimmermann","year":"2008","journal-title":"Histochem. Cell. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.expneurol.2015.08.004","article-title":"\u201cGAG-ing with the neuron\u201d: The role of glycosaminoglycan patterning in the central nervous system","volume":"274","author":"Smith","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1177\/0271678X17722436","article-title":"The vascular basement membrane in the healthy and pathological brain","volume":"37","author":"Thomsen","year":"2017","journal-title":"J. Cerebr. Blood Flow Met."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10545-016-9981-6","article-title":"Newborn screening for mucopolysaccharidoses: A pilot study of measurement of glycosaminoglycans by tandem mass spectrometry","volume":"40","author":"Kubaski","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","first-page":"100563","article-title":"Newborn screening for mucopolysaccharidoses: Measurement of glycosaminoglycans by LC-MS\/MS","volume":"22","author":"Stapleton","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.2147\/COPD.S182731","article-title":"Serum endocan levels in patients with stable COPD","volume":"13","author":"Pihtili","year":"2018","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1093\/infdis\/jiv234","article-title":"Serum Syndecan-4 as a possible biomarker in patients with acute pneumonia","volume":"212","author":"Nikaido","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8194","DOI":"10.1074\/jbc.M113.539452","article-title":"The circulating glycosaminoglycan signature of respiratory failure in critically ill adults","volume":"289","author":"Schmidt","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.resuscitation.2012.01.028","article-title":"Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome","volume":"83","author":"Grundmann","year":"2012","journal-title":"Resuscitation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ymgme.2018.04.011","article-title":"Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis","volume":"125","author":"Khan","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","first-page":"6","article-title":"Assay for glycosaminoglycans by Tandem Mass Spectrometry and its applications","volume":"2014","author":"Tomatsu","year":"2014","journal-title":"J. Anal. Bioanal. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ymgme.2013.06.007","article-title":"Newborn screening and diagnosis of mucopolysaccharidoses","volume":"110","author":"Tomatsu","year":"2013","journal-title":"Minireview Mol. Genet Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ymgme.2016.12.010","article-title":"Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses","volume":"120","author":"Kubaski","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","first-page":"1","article-title":"Di-sulfated keratan sulfate as a novel biomarker for mucopolysaccharidosis II, IVA, and IVB","volume":"21","author":"Shimada","year":"2015","journal-title":"JIMD Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/8904_2014_311","article-title":"Chondroitin 6-sulfate as a novel biomarker for mucopolysaccharidosis IVA and VII","volume":"16","author":"Shimada","year":"2014","journal-title":"JIMD Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.clinthera.2007.07.004","article-title":"Importance of observational studies in clinical practice","volume":"29 Pt 1","author":"Ligthelm","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Celik, B., Tomatsu, S.C., Tomatsu, S., and Khan, S.A. (2021). Epidemiology of mucopolysaccharidoses update. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020273"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/aas.12223","article-title":"Circulating glycosaminoglycans species in septic shock","volume":"58","author":"Nelson","year":"2014","journal-title":"Acta. Anaesthesiol. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymgme.2017.10.006","article-title":"Epilepsy in mucopolysaccharidosis disorders","volume":"122","author":"Scarpa","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0014-4886(03)00251-6","article-title":"Kainic acid-induced convulsions cause prolonged changes in the chondroitin sulfate proteoglycans neurocan and phosphacan in the limbic structures","volume":"184","author":"Okamoto","year":"2003","journal-title":"Exp. Neurobiol."},{"key":"ref_23","first-page":"122","article-title":"Role of glycosaminoglycans for binding and infection of hepatitis B virus","volume":"10","author":"Leistner","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1128\/jvi.63.1.52-58.1989","article-title":"Initial interaction of herpes simplex virus with cells is binding to heparan sulfate","volume":"63","author":"WuDunn","year":"1989","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1161\/STROKEAHA.119.025953","article-title":"Multiple soluble components of the glycocalyx are increased in patient plasma after ischemic stroke","volume":"50","author":"DellaValle","year":"2019","journal-title":"Stroke"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.brainres.2011.11.032","article-title":"Expression of heparanase in vasculature cells and astrocytes of the mouse brain after focal cerebral ischemia","volume":"1433","author":"Li","year":"2012","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1523\/JNEUROSCI.11-11-03398.1991","article-title":"Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes","volume":"11","author":"McKeon","year":"1991","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbrc.2008.02.130","article-title":"Increased expression of highly sulfated keratan sulfate synthesized in malignant astrocytic tumors","volume":"369","author":"Kato","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/j.1471-4159.2005.03632.x","article-title":"Intracellular trafficking in neurons and glia of fibroblast growth factor-2, fibroblast growth factor receptor 1 and heparan sulphate proteoglycans in the injured adult rat cerebral cortex","volume":"96","author":"Leadbeater","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1172\/JCI124485","article-title":"Circulating heparan sulfate fragments mediate septic cognitive dysfunction","volume":"129","author":"Hippensteel","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/SHK.0000000000000462","article-title":"Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes","volume":"44","author":"Peters","year":"2015","journal-title":"Shock"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/9\/1563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:54:32Z","timestamp":1760165672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/9\/1563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["diagnostics11091563"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11091563","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]}}}