{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:16:38Z","timestamp":1792030598878,"version":"4.4.0"},"reference-count":259,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007479","name":"Fondazione Cassa di Risparmio di Padova e Rovigo","doi-asserted-by":"publisher","award":["Bando Ricerca Pediatrica 17_06"],"award-info":[{"award-number":["Bando Ricerca Pediatrica 17_06"]}],"id":[{"id":"10.13039\/100007479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type II (MPS II, Hunter syndrome) was first described by Dr. Charles Hunter in 1917. Since then, about one hundred years have passed and Hunter syndrome, although at first neglected for a few decades and afterwards mistaken for a long time for the similar disorder Hurler syndrome, has been clearly distinguished as a specific disease since 1978, when the distinct genetic causes of the two disorders were finally identified. MPS II is a rare genetic disorder, recently described as presenting an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births, and it is the only X-linked-inherited mucopolysaccharidosis. The complex disease is due to a deficit of the lysosomal hydrolase iduronate 2-sulphatase, which is a crucial enzyme in the stepwise degradation of heparan and dermatan sulphate. This contributes to a heavy clinical phenotype involving most organ-systems, including the brain, in at least two-thirds of cases. In this review, we will summarize the history of the disease during this century through clinical and laboratory evaluations that allowed its definition, its correct diagnosis, a partial comprehension of its pathogenesis, and the proposition of therapeutic protocols. We will also highlight the main open issues related to the possible inclusion of MPS II in newborn screenings, the comprehension of brain pathogenesis, and treatment of the neurological compartment.<\/jats:p>","DOI":"10.3390\/ijms21041258","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T04:06:01Z","timestamp":1582085161000},"page":"1258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":154,"title":["Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2790-6481","authenticated-orcid":false,"given":"Francesca","family":"D\u2019Avanzo","sequence":"first","affiliation":[{"name":"Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women\u2019s and Children \u2018s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0233-1677","authenticated-orcid":false,"given":"Laura","family":"Rigon","sequence":"additional","affiliation":[{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"},{"name":"Molecular Developmental Biology, Life &amp; Medical Science Institute (LIMES), University of Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women\u2019s and Children \u2018s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[{"name":"Laboratory of Diagnosis and Therapy of Lysosomal Disorders, Department of Women\u2019s and Children \u2018s Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy"},{"name":"Fondazione Istituto di Ricerca Pediatrica \u201cCitt\u00e0 della Speranza\u201d, Corso Stati Uniti 4, 35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ymgme.2017.05.016","article-title":"Epidemiology of mucopolysaccharidoses","volume":"121","author":"Khan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1542\/peds.2007-1350","article-title":"Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome)","volume":"121","author":"Martin","year":"2008","journal-title":"Pediatrics"},{"key":"ref_3","first-page":"104","article-title":"A Rare Disease in Two Brothers","volume":"10","author":"Hunter","year":"1917","journal-title":"Proc. R. Soc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3109\/00365515209060631","article-title":"Gargoylism: A mucopolysaccharidosis","volume":"4","author":"Brante","year":"1952","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/BF02222956","article-title":"A type of multiple degeneration that mainly affects the skeletal system","volume":"24","author":"Hurler","year":"1919","journal-title":"Z Kinderheilkd"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/220583b0","article-title":"Hunter\u2013Hurler Syndrome: Gel Filtration and Dialysis of Urinary Acid Mucopolysaccharides","volume":"220","author":"Constantopoulos","year":"1968","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1073\/pnas.60.2.699","article-title":"The defect in Hurler\u2019s and Hunter\u2019s syndromes: Faulty degradation of mucopolysaccharide","volume":"60","author":"Fratantoni","year":"1968","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3928\/00904481-19780201-06","article-title":"The mucopolysaccharidoses: Advances in understanding and treatment","volume":"7","author":"Lorincz","year":"1978","journal-title":"Pediatr. Ann."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1126\/science.162.3853.570","article-title":"Hurler and Hunter syndromes: Mutual correction of the defect in cultured fibroblasts","volume":"162","author":"Fratantoni","year":"1968","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/0006-291X(70)90414-6","article-title":"Characterization of the factor deficient in the Hunter syndrome by polyacrylamide gel electrophoresis","volume":"39","author":"Cantz","year":"1970","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1016\/S0021-9258(20)81127-2","article-title":"The Hunter Corrective Factor","volume":"247","author":"Cantz","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1111\/j.1749-6632.1971.tb46934.x","article-title":"Corrective factors for inborn errors of mucopolysaccharide metabolism","volume":"179","author":"Neufeld","year":"1971","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1073\/pnas.70.7.2134","article-title":"The defect in the Hunter syndrome: Deficiency of sulfoiduronate sulfatase","volume":"70","author":"Bach","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1073\/pnas.87.21.8531","article-title":"Hunter syndrome: Isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA","volume":"87","author":"Wilson","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1006\/geno.1993.1406","article-title":"Sequence of the human iduronate 2-sulfatase (IDS) gene","volume":"17","author":"Wilson","year":"1993","journal-title":"Genomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/hmg\/2.1.5","article-title":"Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene","volume":"2","author":"Flomen","year":"1993","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/BF00225070","article-title":"Evidence for an iduronate-sulfatase pseudogene near the functional Hunter syndrome gene in Xq27.3-q28","volume":"95","author":"Rathmann","year":"1995","journal-title":"Hum. Genet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/hmg\/4.4.615","article-title":"Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome","volume":"4","author":"Bondeson","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","first-page":"A427","article-title":"Targeting disruption of the mouse iduronate sulfatase gene","volume":"65","author":"Muenzer","year":"1999","journal-title":"Am J Genet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ymthe.2006.01.006","article-title":"Gene therapy for lysosomal storage diseases","volume":"13","author":"Sands","year":"2006","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1651-2227.2012.02674.x","article-title":"Gene therapy approaches for lysosomal storage disorders, a good model for the treatment of mendelian diseases","volume":"101","author":"Tomanin","year":"2012","journal-title":"Acta Paediatr. Int. J. Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1042\/bj3090425","article-title":"Processing of iduronate 2-sulphatase in human fibroblasts","volume":"309","author":"Froissart","year":"1995","journal-title":"Biochem. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms15786","article-title":"Insights into Hunter syndrome from the structure of iduronate-2-sulfatase","volume":"8","author":"Demydchuk","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000472302","article-title":"Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational analysis of Hunter syndrome","volume":"3","author":"Bondeson","year":"1995","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","first-page":"1202","article-title":"Mucopolysaccharidosis type II (Hunter syndrome): Mutation \u201chot spots\u201d in the iduronate-2-sulfatase gene","volume":"59","author":"Rathmann","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/hmg\/6.4.627","article-title":"Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome","volume":"6","author":"Lagerstedt","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/sj.ejhg.5200213","article-title":"Homologous nonallelic recombinations between the iduronate-sulfatase gene and pseudogene cause various intragenic deletions and inversions in patients with mucopolysaccharidosis type II","volume":"6","author":"Bunge","year":"1998","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/(SICI)1098-1004(1996)8:1<44::AID-HUMU6>3.0.CO;2-P","article-title":"IDS gene-pseudogene exchange responsible for an intragenic deletion in a Hunter patient","volume":"8","author":"Birot","year":"1996","journal-title":"Hum. Mutat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/hmg\/6.3.479","article-title":"Molecular and phenotypic variation in patients with severe Hunter syndrome","volume":"6","author":"Timms","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","first-page":"21","article-title":"Molecular basis of iduronate-2-sulphatase gene mutations in patients with mucopolysaccharidosis type II (Hunter syndrome)","volume":"36","author":"Li","year":"1999","journal-title":"J. Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10545-009-9023-8","article-title":"Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: Brain magnetic resonance imaging features and evolution","volume":"33","author":"Manara","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/(SICI)1098-1004(1996)7:3<266::AID-HUMU12>3.0.CO;2-0","article-title":"A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient","volume":"7","author":"Birot","year":"1996","journal-title":"Hum. Mutat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/geno.1997.4811","article-title":"Two distinct deletions in the IDS gene and the gene W: A novel type of mutation associated with the Hunter syndrome","volume":"43","author":"Karsten","year":"1997","journal-title":"Genomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1002\/(SICI)1098-1004(200004)15:4<324::AID-HUMU4>3.0.CO;2-5","article-title":"Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): Identification of a fusion transcript including sequences from the gene W and the IDS gene","volume":"15","author":"Lagerstedt","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1093\/bioinformatics\/bty419","article-title":"NGL viewer: Web-based molecular graphics for large complexes","volume":"34","author":"Rose","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.pediatrneurol.2004.10.009","article-title":"Mucopolysaccharidosis type II in females: Case report and review of literature","volume":"32","author":"Tuschl","year":"2005","journal-title":"Pediatr. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1002\/ajmg.a.33589","article-title":"A mother and daughter with the p.R443X mutation of mucopolysaccharidosis type II: Genotype and phenotype analysis","volume":"152A","author":"Sohn","year":"2010","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, H., Li, J., Zhang, X., Wang, Y., Qiu, W., Ye, J., Han, L., Gao, X., and Gu, X. (2011). Analysis of the IDS Gene in 38 Patients with Hunter Syndrome: The c.879G>A (p.Gln293Gln) Synonymous Variation in a Female Create Exonic Splicing. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022951"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1399-0004.2010.01574.x","article-title":"Female Hunter syndrome caused by a single mutation and familial XCI skewing: Implications for other X-linked disorders","volume":"80","author":"Kloska","year":"2011","journal-title":"Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ajmg.a.34415","article-title":"Mucopolysaccharidosis type II in females and response to enzyme replacement therapy","volume":"158 A","author":"Jurecka","year":"2012","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejmg.2012.11.006","article-title":"Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation","volume":"56","author":"Rau","year":"2013","journal-title":"Eur. J. Med. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1002\/ajmg.a.36667","article-title":"Mucopolysaccharidosis type II in a female patient with a reciprocal X;9 translocation and skewed X chromosome inactivation","volume":"164","author":"Lonardo","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1651-2227.2007.00213.x","article-title":"Mucopolysaccharidosis type II: An update on mutation spectrum","volume":"96","author":"Froissart","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/cge.12927","article-title":"Genotype\u2013phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II","volume":"91","author":"Dvorakova","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/dmcn.13467","article-title":"Genotype\u2013phenotype relationship in mucopolysaccharidosis II: Predictive power of IDS variants for the neuronopathic phenotype","volume":"59","author":"Vollebregt","year":"2017","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s00109-006-0057-1","article-title":"Multiple cryptic splice sites can be activated by IDS point mutations generating misspliced transcripts","volume":"84","author":"Lualdi","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"E1261","DOI":"10.1002\/humu.21208","article-title":"Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in hunter syndrome","volume":"31","author":"Lualdi","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ymgme.2013.03.001","article-title":"The effect of idursulfase on growth in patients with Hunter syndrome: Data from the Hunter Outcome Survey (HOS)","volume":"109","author":"Jones","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1017\/S1047951109003576","article-title":"The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses","volume":"19","author":"Corti","year":"2009","journal-title":"Cardiol. Young"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/21678707.2017.1296761","article-title":"Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)","volume":"5","author":"Stapleton","year":"2017","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00431-007-0635-4","article-title":"Mucopolysaccharidosis type II (Hunter syndrome): A clinical review and recommendations for treatment in the era of enzyme replacement therapy","volume":"167","author":"Wraith","year":"2008","journal-title":"Eur. J. Pediatr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13023-014-0129-1","article-title":"Clinical efficacy of Enzyme Replacement Therapy in paediatric Hunter patients, an independent study of 3.5 years","volume":"9","author":"Tomanin","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s11325-014-0944-6","article-title":"Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I, II, and VI in a reference center","volume":"18","author":"Moreira","year":"2014","journal-title":"Sleep Breath."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1258","DOI":"10.1542\/peds.2010-1274","article-title":"Natural progression of neurological disease in mucopolysaccharidosis type II","volume":"127","author":"Holt","year":"2011","journal-title":"Pediatrics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10545-011-9317-5","article-title":"Brain and spine MRI features of Hunter disease: Frequency, natural evolution and response to therapy","volume":"34","author":"Manara","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1007\/s10545-009-1275-9","article-title":"Clinical and biochemical studies in mucopolysaccharidosis type II carriers","volume":"32","author":"Schwartz","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/ajmg.a.33770","article-title":"Are MPS II heterozygotes actually asymptomatic? A study based on clinical and biochemical data, X-inactivation analysis and imaging evaluations","volume":"155","author":"Maluf","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1750-1172-8-92","article-title":"Clinical manifestations in female carriers of mucopolysaccharidosis type II: A spanish cross-sectional study","volume":"8","author":"Couce","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1750-1172-5-14","article-title":"VD Expression of the disease on female carriers of X-linked lysosomal disorders: A brief review","volume":"5","author":"Pinto","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/0003-2697(62)90095-7","article-title":"A modified uronic acid carbazole reaction","volume":"4","author":"Bitter","year":"1962","journal-title":"Anal. Biochem."},{"key":"ref_62","first-page":"419","article-title":"Clinical application of a new simple method for the identification of mucopolysaccharidoses","volume":"42","author":"Coppa","year":"1987","journal-title":"Helv. Paediatr. Acta"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/0009-8981(72)90287-2","article-title":"Sequential thin layer chromatography of urinary acidic glycosaminglycans","volume":"40","author":"Humbel","year":"1972","journal-title":"Clin. Chim. Acta"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s13052-018-0553-2","article-title":"Biochemical and molecular analysis in mucopolysaccharidoses: What a paediatrician must know","volume":"44","author":"Filocamo","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ymgme.2016.09.005","article-title":"Glycosaminoglycans detection methods: Applications of mass spectrometry","volume":"120","author":"Kubaski","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/clinchem\/35.3.374","article-title":"Diagnostic test for mucopolysaccharidosis. I. Direct method for quantifying excessive urinary glycosaminoglycan excretion","volume":"35","author":"Whitley","year":"1989","journal-title":"Clin. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/clinchem\/39.1.163","article-title":"Pitfalls of screening for mucopolysaccharidoses by the dimethylmethylene blue test","volume":"39","author":"Piraud","year":"1993","journal-title":"Clin. Chem."},{"key":"ref_68","unstructured":"Pagon, R.A., Adam, M.P., Ardinger, H.H., Wallace, S.E., Amemiya, A., Bean, L.J.H., Bird, T.D., Fong, C.T., Mefford, H.C., and Smith, R.J.H. (2018). Mucopolysaccharidosis Type II, University of Washington. GeneReviews."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s10545-006-0440-7","article-title":"Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: Enzymatic activity, protein processing and structural analysis","volume":"29","author":"Kato","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/humu.20165","article-title":"Characterization of iduronate-2-sulfatase gene-pseudogene recombinations in eight patients with Mucopolysaccharidosis type II revealed by a rapid PCR-based method","volume":"25","author":"Lualdi","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/8904_2014_317","article-title":"A hunter patient with a severe phenotype reveals two large deletions and two duplications extending 1.2 mb distally to IDS locus","volume":"Volume 17","author":"Zanetti","year":"2014","journal-title":"JIMD Reports"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1750-1172-9-59","article-title":"Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders","volume":"9","author":"Morey","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zanetti, A., D\u2019Avanzo, F., Bertoldi, L., Zampieri, G., Feltrin, E., De Pascale, F., Rampazzo, A., Forzan, M., Valle, G., and Tomanin, R. (2020). Set up and validation of a targeted NGS approach for the diagnosis of lysosomal storage disorders. J. Mol. Diagn., In press.","DOI":"10.1016\/j.jmoldx.2020.01.010"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ymgme.2013.11.015","article-title":"Early initiation of enzyme replacement therapy for the mucopolysaccharidoses","volume":"111","author":"Muenzer","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1097\/ANC.0000000000000569","article-title":"Hunter Syndrome","volume":"18","author":"Joseph","year":"2018","journal-title":"Adv. Neonatal Care"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1373\/clinchem.2014.225771","article-title":"Newborn Screening for Lysosomal Storage Diseases","volume":"61","author":"Gelb","year":"2015","journal-title":"Clin. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1021\/ac102777s","article-title":"Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: Application to screening newborns for mucopolysaccharidosis II (Hunter Syndrome)","volume":"83","author":"Wolfe","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.ymgme.2012.09.024","article-title":"Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III","volume":"107","author":"Wagemans","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1021\/ac5004135","article-title":"Improved reagents for newborn screening of mucopolysaccharidosis types I, II, and VI by tandem mass spectrometry","volume":"86","author":"Chennamaneni","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1373\/clinchem.2015.242560","article-title":"Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI","volume":"61","author":"Kumar","year":"2015","journal-title":"Clin. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1373\/clinchem.2016.269167","article-title":"Multiplex Tandem Mass Spectrometry Enzymatic Activity Assay for Newborn Screening of the Mucopolysaccharidoses and Type 2 Neuronal Ceroid Lipofuscinosis","volume":"63","author":"Liu","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_82","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_83","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jpeds.2018.09.063","article-title":"Taiwan National Newborn Screening Program by Tandem Mass Spectrometry for Mucopolysaccharidoses Types I, II, and VI","volume":"205","author":"Chan","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jpeds.2019.07.053","article-title":"Population-Based Newborn Screening for Mucopolysaccharidosis Type II in Illinois: The First Year Experience","volume":"214","author":"Burton","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_85","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":"Mol. Genet. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Menkovic, I., Marchand, A.S., Boutin, M., and Auray-Blais, C. (2019). Neonatal mass urine screening approach for early detection of mucopolysaccharidoses by UPLC-MS\/MS. Diagnostics, 9.","DOI":"10.3390\/diagnostics9040195"},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"051","DOI":"10.1055\/s-0036-1593843","article-title":"Newborn Screening for Lysosomal Storage Disorders","volume":"06","author":"Peake","year":"2016","journal-title":"J. Pediatr. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1399-0004.2007.00783.x","article-title":"Newborn screening for mucopolysaccharidoses: Opinions of patients and their families","volume":"71","author":"Hayes","year":"2007","journal-title":"Clin. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ymgme.2012.08.008","article-title":"Experiences of parents and patients with the timing of Mucopolysaccharidosis type I (MPS I) diagnoses and its relevance to the ethical debate on newborn screening","volume":"107","author":"Bouwman","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_91","first-page":"226","article-title":"Newborn screening in mucopolysaccharidoses 11 Medical and Health Sciences 1114 Paediatrics and Reproductive Medicine","volume":"44","author":"Donati","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Muenzer, J., Beck, M., Eng, C.M., Escolar, M.L., Giugliani, R., Guffon, N.H., Harmatz, P., Kamin, W., Kampmann, C., and Koseoglu, S.T. (2009). Multidisciplinary management of Hunter syndrome. Pediatrics, 124.","DOI":"10.1542\/peds.2008-0999"},{"key":"ref_93","first-page":"358","article-title":"The nature and impact of neurobehavioral symptoms in neuronopathic Hunter syndrome","volume":"22","author":"Eisengart","year":"2020","journal-title":"Mol. Genet. Metab. Reports"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ymgme.2019.07.016","article-title":"Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England","volume":"129","author":"Broomfield","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_95","unstructured":"Scriver, C.R. (2001). The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s10545-011-9359-8","article-title":"Cardiac disease in patients with mucopolysaccharidosis: Presentation, diagnosis and management","volume":"34","author":"Braunlin","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_97","first-page":"1045","article-title":"From cytases to lysosomes","volume":"23","year":"1964","journal-title":"Fed. Proc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1056\/NEJM196608112750606","article-title":"The sphingolipidoses","volume":"275","author":"Brady","year":"1966","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJM197307052890103","article-title":"Replacement Therapy for Inherited Enzyme Deficiency","volume":"289","author":"Brady","year":"1973","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJM197411072911901","article-title":"Replacement Therapy for Inherited Enzyme Deficiency","volume":"291","author":"Brady","year":"1974","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1039\/9781782624202-00164","article-title":"Discovery and clinical development of idursulfase (Elaprase\u00ae) for the treatment of mucopolysaccharidosis II (Hunter syndrome)","volume":"38","author":"Heartlein","year":"2014","journal-title":"Orphan Drugs Rare Dis."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lagler, F.B. (2019). Current and Emerging Therapies for Mucopolysaccharidoses. Handb. Exp. Pharmacol.","DOI":"10.1007\/164_2019_263"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/jhg.2016.133","article-title":"Comparative study of idursulfase beta and idursulfase in vitro and in vivo","volume":"62","author":"Kim","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10719-014-9523-0","article-title":"A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome","volume":"31","author":"Chung","year":"2014","journal-title":"Glycoconj. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1750-1172-8-42","article-title":"Phase I\/II clinical trial of enzyme replacement therapy with idursulfase beta in patients with mucopolysaccharidosis II (Hunter Syndrome)","volume":"8","author":"Sohn","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ymgme.2006.09.001","article-title":"A phase I\/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome)","volume":"90","author":"Muenzer","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/01.gim.0000232477.37660.fb","article-title":"A phase II\/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)","volume":"8","author":"Muenzer","year":"2006","journal-title":"Genet. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/GIM.0b013e3181fea459","article-title":"Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s10545-014-9686-7","article-title":"Long-term experience with enzyme replacement therapy (ERT) in MPS II patients with a severe phenotype: An international case series","volume":"37","author":"Lampe","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_110","first-page":"65","article-title":"Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients","volume":"3","author":"Parini","year":"2015","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s40265-019-01147-4","article-title":"Therapeutic Options for Mucopolysaccharidoses: Current and Emerging Treatments","volume":"79","author":"Sawamoto","year":"2019","journal-title":"Drugs"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/gim.2017.30","article-title":"Treatment of mucopolysaccharidosis type II (Hunter syndrome): Results from a systematic evidence review","volume":"19","author":"Bradley","year":"2017","journal-title":"Genet. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Xie, H., Chung, J.-K., Mascelli, M.A., and McCauley, T.G. (2015). Pharmacokinetics and bioavailability of a therapeutic enzyme (idursulfase) in cynomolgus monkeys after intrathecal and intravenous administration. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122453"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10545-016-9994-1","article-title":"Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA","volume":"40","author":"King","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_115","first-page":"2","article-title":"Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients","volume":"12","author":"Giugliani","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"60ra89","DOI":"10.1126\/scitranslmed.3001380","article-title":"Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I","volume":"2","author":"Dierenfeld","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10545-008-0980-0","article-title":"Home treatment with elaprase\u00ae and Naglazyme\u00ae is safe in patients with mucopolysaccharidoses types II and VI, respectively","volume":"31","author":"Bagewadi","year":"2008","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1824-7288-39-53","article-title":"Home treatment in paediatric patients with Hunter syndrome: The first Italian experience","volume":"39","author":"Ceravolo","year":"2013","journal-title":"Ital. J. Pediatr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ymgme.2010.06.011","article-title":"Home treatment with intravenous enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II\u2014Data from the Hunter Outcome Survey","volume":"101","author":"Burton","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13052-018-0562-1","article-title":"Enzyme replacement therapy: Efficacy and limitations","volume":"44","author":"Concolino","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_121","first-page":"1036","article-title":"Ethical issues in managing Lysosomal storage disorders in children in low and middle income countries","volume":"33","author":"Afroze","year":"2017","journal-title":"Pakistan J. Med. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00431-011-1606-3","article-title":"The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus","volume":"171","author":"Muenzer","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ymgme.2012.08.013","article-title":"Effect of rapid cessation of enzyme replacement therapy: A report of 5 cases and a review of the literature","volume":"107","author":"Jurecka","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13554-011-0001-y","article-title":"Clinical consequences of reduced dosing schedule during treatment of a patient with Pompe\u2019s disease","volume":"1","year":"2011","journal-title":"Biol. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s10545-018-0221-0","article-title":"The efficacy of intracerebroventricular idursulfase-beta enzyme replacement therapy in mucopolysaccharidosis II murine model: Heparan sulfate in cerebrospinal fluid as a clinical biomarker of neuropathology","volume":"41","author":"Sohn","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/21678707.2018.1487838","article-title":"Intrathecal\/Intracerebroventricular enzyme replacement therapy for the mucopolysaccharidoses: Efficacy, safety, and prospects","volume":"6","author":"Giugliani","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Calias, P., Papisov, M., Pan, J., Savioli, N., Belov, V., Huang, Y., Lotterhand, J., Alessandrini, M., Liu, N., and Fischman, A.J. (2012). CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: Implications for neurological outcomes of lysosomal storage disorder. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030341"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/gim.2015.36","article-title":"A phase I\/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II","volume":"18","author":"Muenzer","year":"2016","journal-title":"Genet. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1016\/j.ymgme.2016.11.249","article-title":"A long-term extension study evaluating intrathecal idursulfase-IT in children with Hunter syndrome and cognitive impairment","volume":"120","author":"Muenzer","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1016\/j.ymgme.2017.12.262","article-title":"Efficacy and safety of intrathecal idursulfase in pediatric patients with mucopolysaccharidosis type II and early cognitive impairment: Design and methods of a controlled, randomized, phase II\/III multicenter study","volume":"123","author":"Muenzer","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/bit.21602","article-title":"Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier","volume":"99","author":"Boado","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Sato, Y., and Okuyama, T. (2020). Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020400"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1002\/bit.25289","article-title":"Insulin receptor antibody-iduronate 2-sulfatase fusion protein: Pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys","volume":"111","author":"Boado","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1124\/dmd.111.042903","article-title":"Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse","volume":"40","author":"Zhou","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.ymthe.2018.02.032","article-title":"A Blood-Brain-Barrier-Penetrating Anti-human Transferrin Receptor Antibody Fusion Protein for Neuronopathic Mucopolysaccharidosis II","volume":"26","author":"Sonoda","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ymthe.2018.12.005","article-title":"Iduronate-2-Sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1\/2 Trial","volume":"27","author":"Okuyama","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ymgme.2015.06.001","article-title":"Human recombinant lysosomal enzymes produced in microorganisms","volume":"116","author":"Mosquera","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_138","first-page":"1786","article-title":"Laboratory scale production of the human recombinant iduronate 2-sulfate sulfatase-Like from Pichia pastoris","volume":"8","year":"2009","journal-title":"African J. Biotechnol."},{"key":"ref_139","first-page":"2871","article-title":"Cloning and shake flask expression of hrIDS-Like in Pichia pastoris","volume":"8","author":"Delgado","year":"2009","journal-title":"African J. Biotechnol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12275-013-2416-2","article-title":"Low-scale expression and purification of an active putative iduronate 2-sulfate sulfatase-Like enzyme from Escherichia coli K12","volume":"51","author":"Barrera","year":"2013","journal-title":"J. Microbiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/bab.1660","article-title":"Production and characterization of a human lysosomal recombinant iduronate-2-sulfatase produced in Pichia pastoris","volume":"65","author":"Pimentel","year":"2018","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_142","first-page":"28","article-title":"Human sulfatase transiently and functionally active expressed in E. coli K12","volume":"13","author":"Lareo","year":"2010","journal-title":"Electron. J. Biotechnol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ymgme.2009.05.006","article-title":"Localized donor cells in brain of a Hunter disease patient after cord blood stem cell transplantation","volume":"98","author":"Araya","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.ymthe.2017.03.025","article-title":"Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications","volume":"25","author":"Biffi","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_145","first-page":"31","article-title":"Bone marrow transplantation in Hunter syndrome: A preliminary report","volume":"22","author":"Warkentin","year":"1986","journal-title":"Birth Defects Orig. Artic. Ser."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2326409818779097","article-title":"Hematopoietic Stem Cell Transplantation in Mucopolysaccharidosis Type II: A Literature Review and Critical Analysis","volume":"6","author":"Barth","year":"2018","journal-title":"J. Inborn Errors Metab. Screen."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ymgme.2012.09.004","article-title":"Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: A nationwide survey in Japan","volume":"107","author":"Tanaka","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.bbmt.2016.08.015","article-title":"Allogeneic Hematopoietic Stem Cell Transplantation in Thirty-Four Pediatric Cases of Mucopolysaccharidosis-A Ten-Year Report from the China Children Transplant Group","volume":"22","author":"Wang","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ymgmr.2017.05.010","article-title":"Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up","volume":"12","author":"Barth","year":"2017","journal-title":"Mol. Genet. Metab. reports"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ymgmr.2014.04.001","article-title":"Impact of Enzyme Replacement Therapy and Hematopoietic Stem Cell Therapy on Growth in Patients with Hunter Syndrome","volume":"1","author":"Patel","year":"2014","journal-title":"Mol. Genet. Metab. reports"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.bbmt.2017.06.020","article-title":"Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II","volume":"23","author":"Kubaski","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e226","DOI":"10.1016\/j.bbmt.2019.02.012","article-title":"Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future","volume":"25","author":"Taylor","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymgme.2017.12.434","article-title":"Gene therapy for Mucopolysaccharidoses","volume":"123","author":"Sawamoto","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1089\/hum.2019.190","article-title":"Gene-Based Approaches to Inherited Neurometabolic Diseases","volume":"30","author":"Poletti","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2222\/jsv.65.27","article-title":"Gene therapy using retrovirus vectors: Vector development and biosafety at clinical trials","volume":"65","author":"Doi","year":"2015","journal-title":"Uirusu"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1089\/hum.1996.7.3-283","article-title":"Preclinical studies of lymphocyte gene therapy for mild Hunter syndrome (mucopolysaccharidosis type II)","volume":"7","author":"Braun","year":"1996","journal-title":"Hum. Gene Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/jgm.316","article-title":"Construction of a high efficiency retroviral vector for gene therapy of Hunter\u2019s syndrome","volume":"5","author":"Hong","year":"2003","journal-title":"J. Gene Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1146\/annurev.genet.37.110801.143717","article-title":"Integration of Adeno-Associated Virus (AAV) and Recombinant AAV Vectors","volume":"38","author":"McCarty","year":"2004","journal-title":"Annu. Rev. Genet."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/sj.gt.3301541","article-title":"Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors","volume":"8","author":"Donsante","year":"2001","journal-title":"Gene Ther."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1038\/mt.2012.197","article-title":"Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity","volume":"20","author":"Rosas","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1128\/jvi.70.5.3227-3234.1996","article-title":"Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors","volume":"70","author":"Ferrari","year":"1996","journal-title":"J. Virol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1038\/sj.gt.3302134","article-title":"Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo","volume":"10","author":"McCarty","year":"2003","journal-title":"Gene Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/mt.2008.171","article-title":"Self-complementary AAV vectors; advances and applications","volume":"16","author":"McCarty","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/hmg\/ddl038","article-title":"Correction of Hunter syndrome in the MPSII mouse model by AAV2\/8-mediated gene delivery","volume":"15","author":"Cardone","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10059-010-0083-2","article-title":"Characterization of a novel mucopolysaccharidosis type II mouse model and recombinant AAV2\/8 vector-mediated gene therapy","volume":"30","author":"Jung","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.86696","article-title":"CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome)","volume":"1","author":"Motas","year":"2016","journal-title":"JCI Insight"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1089\/hum.2016.101","article-title":"Delivery of an Adeno-associated virus vector into cerebrospinal fluid attenuates central nervous system disease in mucopolysaccharidosis type II mice","volume":"27","author":"Hinderer","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/hum.2016.184","article-title":"Prevention of neurocognitive deficiency in mucopolysaccharidosis Type II mice by central nervous system-directed, AAV9-mediated iduronate sulfatase gene transfer","volume":"28","author":"Laoharawee","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1042\/BJ20120146","article-title":"Lentiviral vectors: Basic to translational","volume":"443","author":"Sakuma","year":"2012","journal-title":"Biochem. J."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1093\/hmg\/ddv457","article-title":"Gene therapy for lysosomal storage disorders: A good start","volume":"25","author":"Biffi","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1089\/hum.2014.158","article-title":"Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine Model of Mucopolysaccharidosis Type II","volume":"26","author":"Wakabayashi","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.bbadis.2008.07.001","article-title":"Gene therapy of Hunter syndrome: Evaluation of the efficiency of muscle electro gene transfer for the production and release of recombinant iduronate-2-sulfatase (IDS)","volume":"1782","author":"Friso","year":"2008","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Schneller, J.L., Lee, C.M., Bao, G., and Venditti, C.P. (2017). Genome editing for inborn errors of metabolism: Advancing towards the clinic. BMC Med., 15.","DOI":"10.1186\/s12916-017-0798-4"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1182\/blood-2014-12-615492","article-title":"In vivo genome editing of the albumin locus as a platform for protein replacement therapy","volume":"126","author":"Sharma","year":"2015","journal-title":"Blood"},{"key":"ref_175","unstructured":"(2020, January 16). First in Vivo Human Genome Editing Trial. Available online: https:\/\/www.nature.com\/articles\/nbt0118-5b."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nbt1018-907","article-title":"Sangamo\u2019s landmark genome editing trial gets mixed reception","volume":"36","author":"Sheridan","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1073\/pnas.68.2.303","article-title":"Induced degradation of glycosaminoglycans in Hurler\u2019s and Hunter\u2019s syndromes by plasma infusion","volume":"68","author":"Nichols","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1073\/pnas.68.8.1738","article-title":"Effect of leukocyte transfusion in a child with type II mucopolysaccharidosis","volume":"68","author":"Knudson","year":"1971","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/257609a0","article-title":"Increased breakdown of glycosaminoglycans and appearance of corrective enzyme after skin transplants in Hunter syndrome","volume":"257","author":"Dean","year":"1975","journal-title":"Nature"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/261323a0","article-title":"Enzyme replacement therapy by fibroblast transplantation in a case of Hunter syndrome","volume":"261","author":"Dean","year":"1976","journal-title":"Nature"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/BF02338973","article-title":"A clinical trial of fibroblast transplantation for the treatment of mucopolysaccharidoses","volume":"6","author":"Gibbs","year":"1983","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01800340","article-title":"Attempted enzyme replacement using human amnion membrane implantations in mucopolysaccharidoses","volume":"15","author":"Muenzer","year":"1992","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/jgm.790","article-title":"Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts","volume":"7","author":"Friso","year":"2005","journal-title":"J. Gene Med."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Salvalaio, M., Rigon, L., Belletti, D., D\u2019Avanzo, F., Pederzoli, F., Ruozi, B., Marin, O., Vandelli, M.A., Forni, F., and Scarpa, M. (2016). Targeted polymeric nanoparticles for brain delivery of high molecular weight molecules in lysosomal storage disorders. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156452"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Rigon, L., Salvalaio, M., Pederzoli, F., Legnini, E., Duskey, J.T., D\u2019Avanzo, F., De Filippis, C., Ruozi, B., Marin, O., and Vandelli, M.A. (2019). Targeting brain disease in MPSII: Preclinical evaluation of IDS-loaded PLGA nanoparticles. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082014"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Coutinho, M.F., Santos, J.I., and Alves, S. (2016). Less is more: Substrate reduction therapy for lysosomal storage disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071065"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/sj.ejhg.5201623","article-title":"Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses","volume":"14","author":"Piotrowska","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1476-5381.2009.00565.x","article-title":"Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II","volume":"159","author":"Friso","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1002\/ajmg.a.34146","article-title":"Improvement in the range of joint motion in seven patients with mucopolysaccharidosis type II during experimental gene expression-targeted isoflavone therapy (GET IT)","volume":"155","author":"Marucha","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1423-0127-16-26","article-title":"Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway","volume":"16","author":"Piotrowska","year":"2009","journal-title":"J. Biomed. Sci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.gene.2016.03.029","article-title":"Cell cycle is disturbed in mucopolysaccharidosis type II fi broblasts, and can be improved by genistein","volume":"585","author":"Moskot","year":"2016","journal-title":"Gene"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/mt.2015.62","article-title":"Pharmacological chaperone therapy: Preclinical development, clinical translation, and prospects for the treatment of lysosomal storage disorders","volume":"23","author":"Parenti","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"15912","DOI":"10.1073\/pnas.2536657100","article-title":"Chemical chaperone therapy for brain pathology in G M1-gangliosidosis","volume":"100","author":"Matsuda","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/acn3.292","article-title":"Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study","volume":"3","author":"Narita","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1056\/NEJMoa1510198","article-title":"Treatment of Fabry\u2019s disease with the pharmacologic chaperone migalastat","volume":"375","author":"Germain","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Losada D\u00edaz, J.C., Cepeda Del Castillo, J., Rodriguez-L\u00f3pez, E.A., and Alm\u00e9ciga-D\u00edaz, C.J. (2019). Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints201910.0365.v1"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nbt1018-913","article-title":"FDA approves Galafold, a triumph for Amicus","volume":"36","author":"Moran","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41419-018-0871-8","article-title":"Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II","volume":"9","author":"Osaki","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ymgme.2017.12.428","article-title":"Chaperone effect of sulfated disaccharide from heparin on mutant iduronate-2-sulfatase in mucopolysaccharidosis type II","volume":"123","author":"Hoshina","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1093\/hmg\/ddy131","article-title":"FGF signaling deregulation is associated with early developmental skeletal defects in animal models for mucopolysaccharidosis type II (MPSII)","volume":"27","author":"Bellesso","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"R119","DOI":"10.1093\/hmg\/ddy155","article-title":"The pathogenesis of lysosomal storage disorders: Beyond the engorgement of lysosomes to abnormal development and neuroinflammation","volume":"27","author":"Fiorenza","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1126\/science.149.3687.987","article-title":"Hurler\u2019s syndrome: Demonstration of an inherited disorder of connective tissue in cell culture","volume":"149","author":"Danes","year":"1966","journal-title":"Science"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.123.1.1","article-title":"Hurler\u2019s syndrome. A genetic study in cell culture","volume":"123","author":"Danes","year":"1966","journal-title":"J. Exp. Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1006\/excr.1996.3435","article-title":"IDS Transfer from Overexpressing Cells to IDS-Deficient Cells","volume":"367","author":"Millat","year":"1997","journal-title":"Exp. Cell Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0925-4439(02)00166-7","article-title":"Di Uptake of recombinant iduronate-2-sulfatase into neuronal and glial cells in vitro","volume":"1588","author":"Daniele","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"9378","DOI":"10.1038\/srep09378","article-title":"Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids","volume":"5","author":"Moskot","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Mazzoccoli, G., Tomanin, R., Mazza, T., D\u2019Avanzo, F., Salvalaio, M., Rigon, L., Zanetti, A., Pazienza, V., Francavilla, M., and Giuliani, F. (2013). Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and impact of iduronate-2-sulfatase treatment. BMC Med. Genomics, 6.","DOI":"10.1186\/1755-8794-6-37"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e906","DOI":"10.1038\/cddis.2013.430","article-title":"Murine neural stem cells model Hunter disease in vitro: Glial cell-mediated neurodegeneration as a possible mechanism involved","volume":"4","author":"Zalfa","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"e2331","DOI":"10.1038\/cddis.2016.231","article-title":"Glial degeneration with oxidative damage drives neuronal demise in MPSII disease","volume":"7","author":"Zalfa","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.scr.2016.09.033","article-title":"Generation of Mucopolysaccharidosis type II (MPS II) human induced pluripotent stem cell (iPSC) line from a 1-year-old male with pathogenic IDS mutation","volume":"17","author":"Varga","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.scr.2016.09.032","article-title":"Generation of Mucopolysaccharidosis type II (MPS II) human induced pluripotent stem cell (iPSC) line from a 3-year-old male with pathogenic IDS mutation","volume":"17","author":"Varga","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.scr.2016.09.034","article-title":"Generation of Mucopolysaccharidosis type II (MPS II) human induced pluripotent stem cell (iPSC) line from a 7-year-old male with pathogenic IDS mutation","volume":"17","author":"Varga","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.scr.2016.09.035","article-title":"Generation of human induced pluripotent stem cell (iPSC) line from an unaffected female carrier of Mucopolysaccharidosis type II (MPS II) disorder","volume":"17","author":"Varga","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"101451","DOI":"10.1016\/j.scr.2019.101451","article-title":"Generation of an induced pluripotent stem cell line (TRNDi008-A) from a Hunter syndrome patient carrying a hemizygous 208insC mutation in the IDS gene","volume":"37","author":"Hong","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10545-017-0108-5","article-title":"Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II","volume":"41","author":"Sikora","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.yexcr.2019.04.021","article-title":"Modelling the neuropathology of lysosomal storage disorders through disease-specific human induced pluripotent stem cells","volume":"380","author":"Varga","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nature01262","article-title":"Initial sequencing and comparative analysis of the mouse genome","volume":"420","author":"Consortium","year":"2002","journal-title":"Nature"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1651-2227.2002.tb03118.x","article-title":"Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): A preliminary report","volume":"91","author":"Muenzer","year":"2002","journal-title":"Acta Paediatr. Suppl."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1007\/s10545-007-0641-8","article-title":"The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome)","volume":"30","author":"Garcia","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1177\/030098589803500311","article-title":"Clinical and Morphologic Features of Mucopolysaccharidosis Type II in a Dog: Naturally Occurring Model of Hunter Syndrome","volume":"35","author":"Wilkerson","year":"1998","journal-title":"Vet Pathol"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.matbio.2009.09.001","article-title":"A novel functional role of iduronate-2-sulfatase in zebrafish early development","volume":"29","author":"Moro","year":"2010","journal-title":"Matrix Biol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ymgme.2012.05.005","article-title":"Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II","volume":"107","author":"Higuchi","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"46","DOI":"10.15252\/emmm.201708730","article-title":"Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms","volume":"10","author":"Gleitz","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00216-016-0076-x","article-title":"Multimodal detection of GM2 and GM3 lipid species in the brain of mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and immunohistochemistry","volume":"409","author":"Dufresne","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0172435","article-title":"Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of mucopolysaccharidosis type II","volume":"12","author":"Gleitz","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11011-017-0110-5","article-title":"Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model","volume":"33","author":"Azambuja","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Salvalaio, M., D\u2019Avanzo, F., Rigon, L., Zanetti, A., D\u2019Angelo, M., Valle, G., Scarpa, M., and Tomanin, R. (2017). Brain RNA-seq profiling of the mucopolysaccharidosis type II mouse model. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18051072"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3349\/ymj.2011.52.2.263","article-title":"Changes in glycogen and glycosaminoglycan levels in hepatocytes of iduronate-2-sulfatase knockout mice before and after recombinant iduronate-2-sulfatase supplementation","volume":"52","author":"Lee","year":"2011","journal-title":"Yonsei Med. J."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1002\/ajmg.a.35498","article-title":"Auditory characteristics and therapeutic effects of enzyme replacement in mouse model of the mucopolysaccharidosis (MPS) II","volume":"158 A","author":"Hong","year":"2012","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Maeda, M., Seto, T., Kadono, C., Morimoto, H., Kida, S., Suga, M., Nakamura, M., Kataoka, Y., Hamazaki, T., and Shintaku, H. (2019). Autophagy in the Central Nervous System and Effects of Chloroquine in Mucopolysaccharidosis Type II Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235829"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ymgme.2007.03.003","article-title":"Preclinical dose ranging studies for enzyme replacement therapy with idursulfase in a knock-out mouse model of MPS II","volume":"91","author":"Garcia","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/jhg.2013.92","article-title":"High-dose enzyme replacement therapy attenuates cerebroventriculomegaly in a mouse model of mucopolysaccharidosis type II","volume":"58","author":"Ahn","year":"2013","journal-title":"J. Hum. Genet."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/ajmg.a.35869","article-title":"Improvement of CNS defects via continuous intrathecal enzyme replacement by osmotic pump in mucopolysaccharidosis type II mice","volume":"161A","author":"Sohn","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ymgme.2013.09.013","article-title":"Enzyme augmentation therapy enhances the therapeutic efficacy of bone marrow transplantation in mucopolysaccharidosis type II mice","volume":"111","author":"Akiyama","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13023-015-0356-0","article-title":"Effect of systemic high dose enzyme replacement therapy on the improvement of CNS defects in a mouse model of mucopolysaccharidosis type II","volume":"10","author":"Cho","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ajhg.2009.07.011","article-title":"IDS Crossing of the Blood-Brain Barrier Corrects CNS Defects in MPSII Mice","volume":"85","author":"Polito","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10545-014-9800-x","article-title":"Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II","volume":"38","author":"Yokoi","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ymgme.2016.08.003","article-title":"Non-myeloablative preconditioning with ACK2 (anti-c-kit antibody) is efficient in bone marrow transplantation for murine models of mucopolysaccharidosis type II","volume":"119","author":"Yokoi","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.ymthe.2018.03.002","article-title":"Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-Mediated In Vivo Genome Editing","volume":"26","author":"Laoharawee","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ymgme.2015.05.009","article-title":"A method for measuring disease-specific iduronic acid from the non-reducing end of glycosaminoglycan in mucopolysaccharidosis type II mice","volume":"117","author":"Shimada","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4155\/bio-2018-0306","article-title":"Distribution of heparan sulfate and dermatan sulfate in mucopolysaccharidosis type II mouse tissues pre- and post-enzyme-replacement therapy determined by UPLC\u2013MS\/MS","volume":"11","author":"Menkovic","year":"2019","journal-title":"Bioanalysis"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"37515","DOI":"10.1074\/jbc.M111.287474","article-title":"Mucopolysaccharidosis type I, unique structure of accumulated heparan sulfate and increased N-sulfotransferase activity in mice lacking alpha-l-iduronidase","volume":"286","author":"Holley","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1093\/hmg\/ddx069","article-title":"Perturbations in cell signaling elicit early cardiac defects in mucopolysaccharidosis type II","volume":"26","author":"Costa","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"12238","DOI":"10.1021\/acs.analchem.5b03232","article-title":"Proteomic Discovery and Development of a Multiplexed Targeted MRM-LC-MS\/MS Assay for Urine Biomarkers of Extracellular Matrix Disruption in Mucopolysaccharidoses I, II, and VI","volume":"87","author":"Heywood","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ymgme.2012.05.003","article-title":"Biomarkers for the mucopolysaccharidoses: Discovery and clinical utility","volume":"106","author":"Clarke","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ymgme.2013.07.016","article-title":"Glycan-based biomarkers for mucopolysaccharidoses","volume":"111","author":"Lawrence","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.jpeds.2008.11.005","article-title":"Improved Metabolic Correction in Patients with Lysosomal Storage Disease Treated with Hematopoietic Stem Cell Transplant Compared with Enzyme Replacement Therapy","volume":"154","author":"Wynn","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1096-7192(03)00018-0","article-title":"Determination of monosaccharides and disaccharides in mucopolysaccharidoses patients by electrospray ionisation mass spectrometry","volume":"78","author":"Ramsay","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ymgme.2009.10.001","article-title":"Validation of disaccharide compositions derived from dermatan sulfate and heparan sulfate in mucopolysaccharidoses and mucolipidoses II and III by tandem mass spectrometry","volume":"99","author":"Tomatsu","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_250","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_251","first-page":"100455","article-title":"Biomarkers in patients with mucopolysaccharidosis type II and IV","volume":"19","author":"Fujitsuka","year":"2019","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"825","DOI":"10.4155\/bio-2018-0025","article-title":"A novel LC-MS\/MS assay to quantify dermatan sulfate in cerebrospinal fluid as a biomarker for mucopolysaccharidosis II","volume":"10","author":"Pan","year":"2018","journal-title":"Bioanalysis"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nchembio.766","article-title":"Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses","volume":"8","author":"Lawrence","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_254","first-page":"257","article-title":"Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ymgme.2008.05.001","article-title":"Heparin cofactor II-thrombin complex: A biomarker of MPS disease","volume":"94","author":"Randall","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10545-010-9254-8","article-title":"Heparin cofactor II-thrombin complex and dermatan sulphate: Chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases","volume":"34","author":"Mercer","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10545-011-9369-6","article-title":"Longitudinal observations of serum heparin cofactor II-thrombin complex in treated Mucopolysaccharidosis i and II patients","volume":"35","author":"Clarke","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_258","doi-asserted-by":"crossref","unstructured":"Patel, N., Mills, P., Davison, J., Cleary, M., Gissen, P., Banushi, B., Doykov, I., Dorman, M., Mills, K., and Heywood, W.E. (2019). Free urinary glycosylated hydroxylysine as an indicator of altered collagen degradation in the mucopolysaccharidoses. J. Inherit. Metab. Dis.","DOI":"10.1002\/jimd.12166"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cca.2019.08.027","article-title":"Proteomic approaches in the discovery of potential urinary biomarkers of mucopolysaccharidosis type II","volume":"499","author":"Yuan","year":"2019","journal-title":"Clin. Chim. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:38Z","timestamp":1760173058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/4\/1258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,13]]},"references-count":259,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21041258"],"URL":"https:\/\/doi.org\/10.3390\/ijms21041258","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,13]]}}}