{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T19:53:03Z","timestamp":1778356383461,"version":"3.51.4"},"reference-count":273,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Comitato Maria Letizia Verga"},{"name":"Fondazione Tettamanti Menotti De Marchi"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucopolysaccharidosis type I (MPSI) (OMIM #252800) is an autosomal recessive disorder caused by pathogenic variants in the IDUA gene encoding for the lysosomal alpha-L-iduronidase enzyme. The deficiency of this enzyme causes systemic accumulation of glycosaminoglycans (GAGs). Although disease manifestations are typically not apparent at birth, they can present early in life, are progressive, and include a wide spectrum of phenotypic findings. Among these, the storage of GAGs within the lysosomes disrupts cell function and metabolism in the cartilage, thus impairing normal bone development and ossification. Skeletal manifestations of MPSI are often refractory to treatment and severely affect patients\u2019 quality of life. This review discusses the pathological and molecular processes leading to impaired endochondral ossification in MPSI patients and the limitations of current therapeutic approaches. Understanding the underlying mechanisms responsible for the skeletal phenotype in MPSI patients is crucial, as it could lead to the development of new therapeutic strategies targeting the skeletal abnormalities of MPSI in the early stages of the disease.<\/jats:p>","DOI":"10.3390\/ijms231911168","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T21:10:05Z","timestamp":1663881005000},"page":"11168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["MPSI Manifestations and Treatment Outcome: Skeletal Focus"],"prefix":"10.3390","volume":"23","author":[{"given":"Giada","family":"De Ponti","sequence":"first","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-758X","authenticated-orcid":false,"given":"Samantha","family":"Donsante","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Frigeni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Metabolism, Zucker School of Medicine at Hofstra\/Northwell, New York, NY 11021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Pievani","sequence":"additional","affiliation":[{"name":"Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-4509","authenticated-orcid":false,"given":"Alessandro","family":"Corsi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Ester","family":"Bernardo","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Pediatrics Department, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-9211","authenticated-orcid":false,"given":"Mara","family":"Riminucci","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Serafini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Metabolism, Zucker School of Medicine at Hofstra\/Northwell, New York, NY 11021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","unstructured":"Sakuru, R., and Bollu, P.C. (2022). Hurler Syndrome. StatPearls, StatPearls Publishing."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s004399900075","article-title":"The frequency of lysosomal storage diseases in The Netherlands","volume":"105","author":"Poorthuis","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/cge.13583","article-title":"Genotype-phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry","volume":"96","author":"Clarke","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/0002-9394(62)93395-0","article-title":"A Newly Recognized Forme Fruste of Hurler\u2019s Disease (Gargoylism)* *From the Departments of Ophthalmology, Dermatology, and Pediatrics, Hospital of the University of Pennsylvania, Children\u2019s Hospital of Philadelphia, and University of Pennsylvania Medical School","volume":"53","author":"Gifford","year":"1962","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1542\/peds.2008-0416","article-title":"The international consensus panel on the management and treatment of mucopolysaccharidosis I mucopolysaccharidosis I: Management and treatment guidelines","volume":"123","author":"Muenzer","year":"2009","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0022-3476(66)80341-4","article-title":"Hurler\u2019s syndrome","volume":"69","author":"Blattner","year":"1966","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.jpeds.2004.01.052","article-title":"The mucopolysaccharidoses: A heterogeneous group of disorders with variable pediatric presentations","volume":"144","author":"Muenzer","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_9","unstructured":"(2022, September 16). Available online: https:\/\/Databases.Lovd.Nl\/Shared\/Genes\/IDUA."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00615","DOI":"10.1002\/mgg3.615","article-title":"\u201cMissing mutations\u201d in MPS I: Identification of two novel copy number variations by an IDUA -specific in house MLPA assay","volume":"7","author":"Jahic","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"\u00c7elik, B., Tomatsu, S.C., Tomatsu, S., and Khan, S.A. (2021). Epidemiology of Mucopolysaccharidoses Update. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020273"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"783644","DOI":"10.3389\/fmolb.2021.783644","article-title":"Mucopolysaccharidosis Type I in the Russian Federation and Other Republics of the Former Soviet Union: Molecular Genetic Analysis and Epidemiology","volume":"8","author":"Voskoboeva","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/hmg\/3.6.861","article-title":"Mucopolysaccharidosis type I: Identification of 8 novel mutations and determination of the frequency of the two common \u03b1-L-iduronidase mutations (W402X and Q70X) among European patients","volume":"3","author":"Bunge","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1006\/mgme.1998.2745","article-title":"Molecular Genetics of Mucopolysaccharidosis Type I: Mutation Analysis among the Patients of the Former Soviet Union","volume":"65","author":"Voskoboeva","year":"1998","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/cge.13224","article-title":"Worldwide distribution of common IDUA pathogenic variants","volume":"94","author":"Poletto","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1046\/j.1469-1809.1999.6310009.x","article-title":"Mucopolysaccharidosis type I: Characterization of a common mutation that causes Hurler syndrome in Moroccan subjects","volume":"63","author":"Alif","year":"1999","journal-title":"Ann. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1746-1596-6-39","article-title":"Molecular analysis of mucopolysaccharidosis type I in Tunisia: Identification of novel mutation and eight Novel polymorphisms","volume":"6","author":"Chkioua","year":"2011","journal-title":"Diagn. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tebani, A., Zanoutene-Cheriet, L., Adjtoutah, Z., Abily-Donval, L., Brasse-Lagnel, C., Laquerri\u00e8re, A., Marret, S., Benabdellah, A.C., and Bekri, S. (2016). Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050743"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/ajmg.a.38551","article-title":"Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis type II: Data from the Hunter Outcome Survey (HOS)","volume":"176","author":"Ficicioglu","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3510","DOI":"10.1002\/ajmg.a.62469","article-title":"The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report","volume":"185","author":"Frigeni","year":"2021","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13023-017-0583-7","article-title":"Early disease progression of Hurler syndrome","volume":"12","author":"Kiely","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1136\/archdischild-2020-319040","article-title":"Improvement in time to treatment, but not time to diagnosis, in patients with mucopolysaccharidosis type I","volume":"106","author":"Giugliani","year":"2021","journal-title":"Arch. Dis. Child."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-3-662-55833-1","article-title":"Lysosomal Storage Disorders in Nonimmune Hydrops Fetalis (NIHF): An Indian Experience","volume":"Volume 35","author":"Morava","year":"2017","journal-title":"JIMD Reports"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-017-0733-y","article-title":"Failure to shorten the diagnostic delay in two ultra-orphan diseases (mucopolysaccharidosis types I and III): Potential causes and implications","volume":"13","author":"Kuiper","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tomatsu, S., Pitz, S., and Hampel, U. (2019). Ophthalmological Findings in Mucopolysaccharidoses. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091467"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.prrv.2010.10.005","article-title":"Respiratory Manifestations in Mucopolysaccharidoses","volume":"12","author":"Muhlebach","year":"2011","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1750-1172-7-22","article-title":"Capturing phenotypic heterogeneity in MPS I: Results of an international consensus procedure","volume":"7","author":"Teunissen","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jpeds.2016.11.036","article-title":"Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management","volume":"182","author":"Clarke","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1651-2227.1995.tb13640.x","article-title":"The presenting features of mucopolysaccharidosis type IH (Hurler syndrome)","volume":"84","author":"Cleary","year":"1995","journal-title":"Acta Paediatr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13023-018-0817-3","article-title":"Beneath the floor: Re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome","volume":"13","author":"Shapiro","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13052-018-0550-5","article-title":"Mucopolysaccharidoses: Early diagnostic signs in infants and children","volume":"44","author":"Galimberti","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1750-1172-3-24","article-title":"The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK","volume":"3","author":"Moore","year":"2008","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF02396619","article-title":"Radiological findings in patients with mucopolysaccharidosis I H\/S (Hurler-Scheie syndrome)","volume":"17","author":"Schmidt","year":"1987","journal-title":"Pediatr. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1002\/ajmg.a.61378","article-title":"Growth patterns for untreated individuals with MPS I: Report from the international MPS I registry","volume":"179","author":"Viskochil","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"839391","DOI":"10.3389\/fcvm.2022.839391","article-title":"Non-cardiac Manifestations in Adult Patients with Mucopolysaccharidosis","volume":"9","author":"Stepien","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Amendum, P.C., Khan, S., Yamaguchi, S., Kobayashi, H., Ago, Y., Suzuki, Y., Celik, B., Rintz, E., Hossain, J., and Xiao, W. (2021). Glycosaminoglycans as Biomarkers for Mucopolysaccharidoses and Other Disorders. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091563"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.omtm.2018.05.002","article-title":"Targeting Heparan Sulfate Proteoglycans as a Novel Therapeutic Strategy for Mucopolysaccharidoses","volume":"10","author":"Sarogni","year":"2018","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10545-009-9036-3","article-title":"Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I","volume":"33","author":"Tomatsu","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ymgme.2020.03.004","article-title":"Advances in glycosaminoglycan detection","volume":"130","author":"Khan","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_41","first-page":"215","article-title":"Age-related changes in glycosaminoglycans of human intervertebral discs","volume":"31","author":"Olczyk","year":"1993","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/glycob\/cwz109","article-title":"Characterization of disease-specific chondroitin sulfate nonreducing end accumulation in mucopolysaccharidosis IVA","volume":"30","author":"Lawrence","year":"2020","journal-title":"Glycobiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1083\/jcb.106.2.423","article-title":"Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix","volume":"106","author":"Saunders","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8544","DOI":"10.1016\/S0021-9258(18)42478-7","article-title":"Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2\/perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor","volume":"267","author":"Murdoch","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.2741\/3578","article-title":"Heparan sulfate proteoglycans in extravasation: Assisting leukocyte guidance","volume":"14","author":"Johanna","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.matbio.2018.06.001","article-title":"Defective collagen proteostasis and matrix formation in the pathogenesis of lysosomal storage disorders","volume":"71\u201372","author":"Settembre","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10545-013-9613-3","article-title":"Mucopolysaccharide diseases: A complex interplay between neuroinflammation, microglial activation and adaptive immunity","volume":"37","author":"Archer","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1203\/01.PDR.0000156510.96253.5A","article-title":"Joint and Bone Disease in Mucopolysaccharidoses VI and VII: Identification of New Therapeutic Targets and BioMarkers Using Animal Models","volume":"57","author":"Simonaro","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2353\/ajpath.2008.070564","article-title":"Mechanism of Glycosaminoglycan-Mediated Bone and Joint Disease: Implications for the Mucopolysaccharidoses and Other Connective Tissue Diseases","volume":"172","author":"Simonaro","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/1746","article-title":"Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice","volume":"20","author":"Xu","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular matrix assembly: A multiscale deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fcell.2017.00106","article-title":"Mitochondria and Lysosomes: Discovering Bonds","volume":"5","author":"Todkar","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.celrep.2017.01.052","article-title":"An Endosomal NAADP-Sensitive Two-Pore Ca 2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling","volume":"18","author":"Kilpatrick","year":"2017","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"903","DOI":"10.4161\/auto.19653","article-title":"MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB","volume":"8","author":"Martina","year":"2012","journal-title":"Autophagy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/hmg\/ddm289","article-title":"A block of autophagy in lysosomal storage disorders","volume":"17","author":"Settembre","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.4161\/cc.25825","article-title":"Regulation of lysosome biogenesis and functions in osteoclasts","volume":"12","author":"Lacombe","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"19678","DOI":"10.1074\/jbc.M802517200","article-title":"Lysosome Dispersion in Osteoblasts Accommodates Enhanced Collagen Production during Differentiation","volume":"283","author":"Nabavi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.job.2017.01.004","article-title":"New functions of lysosomes in bone cells","volume":"59","author":"Tsukuba","year":"2017","journal-title":"J. Oral Biosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1080\/15548627.2016.1190072","article-title":"Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A","volume":"12","author":"Fdez","year":"2016","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cca.2007.09.008","article-title":"Mutational and oxidative stress analysis in patients with mucopolysaccharidosis type I undergoing enzyme replacement therapy","volume":"387","author":"Pereira","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jcp.22039","article-title":"Evidence of lysosomal membrane permeabilization in mucopolysaccharidosis type I: Rupture of calcium and proton homeostasis","volume":"223","author":"Pereira","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10571-008-9335-5","article-title":"Alterations in Oxidative Markers in the Cerebellum and Peripheral Organs in MPS I Mice","volume":"29","author":"Reolon","year":"2009","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wilkinson, F.L., Holley, R.J., Langford-Smith, K.J., Badrinath, S., Liao, A., Langford-Smith, A., Cooper, J.D., Jones, S.A., Wraith, J.E., and Wynn, R.F. (2012). Neuropathology in Mouse Models of Mucopolysaccharidosis Type I, IIIA and IIIB. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035787"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Viana, G.M., Priestman, D.A., Platt, F.M., Khan, S., Tomatsu, S., and Pshezhetsky, A.V. (2020). Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020396"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Breiden, B., and Sandhoff, K. (2020). Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072566"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1242\/dev.33.3.581","article-title":"An analysis of the condensation process during chondrogenesis in the embryonic chick hind limb","volume":"33","author":"Thorogood","year":"1975","journal-title":"Development"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12097","DOI":"10.1073\/pnas.1302703111","article-title":"Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation","volume":"111","author":"Yang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"a008334","DOI":"10.1101\/cshperspect.a008334","article-title":"Development of the Endochondral Skeleton","volume":"5","author":"Long","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.devcel.2010.07.010","article-title":"Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels","volume":"19","author":"Maes","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biocel.2007.06.009","article-title":"Endochondral ossification: How cartilage is converted into bone in the developing skeleton","volume":"40","author":"Mackie","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1101\/gad.1017802","article-title":"The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1093\/emboj\/17.19.5718","article-title":"A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene","volume":"17","author":"Lefebvre","year":"1998","journal-title":"EMBO J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"75","DOI":"10.11005\/jbm.2017.24.2.75","article-title":"Transcriptional Network Controlling Endochondral Ossification","volume":"24","author":"Hata","year":"2017","journal-title":"J. Bone Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1172\/JCI34174","article-title":"Regulation of chondrogenesis and chondrocyte differentiation by stress","volume":"118","author":"Zuscik","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/ng0195-15","article-title":"The Sty-Related Gene Sox9 Is Expressed during Chondrogenesis in Mouse Embryos","volume":"9","author":"Wright","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/8792","article-title":"Sox9 is required for cartilage formation","volume":"22","author":"Bi","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1242\/dev.045203","article-title":"SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification","volume":"137","author":"Hattori","year":"2010","journal-title":"Development"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Leung, V.Y.L., Gao, B., Leung, K.K.H., Melhado, I.G., Wynn, S.L., Au, T.Y.K., Dung, N.W.F., Lau, J.Y.B., Mak, A.C.Y., and Chan, D. (2011). SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002356"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.devcel.2011.12.024","article-title":"Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes","volume":"22","author":"Dy","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1242\/dev.00324","article-title":"Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation","volume":"130","author":"Yang","year":"2003","journal-title":"Development"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1101\/gad.1171104","article-title":"Interactions between Sox9 and \u03b2-catenin control chondrocyte differentiation","volume":"18","author":"Akiyama","year":"2004","journal-title":"Genes Dev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1074\/jbc.M808048200","article-title":"Sox9 Inhibits Wnt Signaling by Promoting \u03b2-Catenin Phosphorylation in the Nucleus","volume":"284","author":"Topol","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0092-8674(00)80257-3","article-title":"Osf2\/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation","volume":"89","author":"Ducy","year":"1997","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"19004","DOI":"10.1073\/pnas.0605170103","article-title":"Dominance of SOX9 function over RUNX2 during skeletogenesis","volume":"103","author":"Zhou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1002\/jbmr.174","article-title":"SOX9 determines RUNX2 transactivity by directing intracellular degradation","volume":"25","author":"Cheng","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1101\/gad.13.16.2072","article-title":"Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation","volume":"13","author":"Hammerschmidt","year":"1999","journal-title":"Genes Dev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1242\/dev.128.24.5099","article-title":"Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation","volume":"128","author":"Long","year":"2001","journal-title":"Development"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1126\/science.273.5275.613","article-title":"Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein","volume":"273","author":"Vortkamp","year":"1996","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1126\/science.273.5275.663","article-title":"PTH\/PTHrP Receptor in Early Development and Indian Hedgehog\u2014Regulated Bone Growth","volume":"273","author":"Lanske","year":"1996","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1172\/JCI11706","article-title":"Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development","volume":"107","author":"Chung","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1172\/JCI24397","article-title":"Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP","volume":"115","author":"Kobayashi","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ydbio.2007.05.011","article-title":"Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage","volume":"308","author":"Hilton","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.bone.2009.09.009","article-title":"Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH\/PTHrP receptor","volume":"46","author":"Maeda","year":"2010","journal-title":"Bone"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1242\/dev.127.3.543","article-title":"Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways","volume":"127","author":"Karp","year":"2000","journal-title":"Development"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10240","DOI":"10.1073\/pnas.93.19.10240","article-title":"Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation","volume":"93","author":"Weir","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5109","DOI":"10.1210\/endo.137.11.8895385","article-title":"Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development","volume":"137","author":"Lee","year":"1996","journal-title":"Endocrinology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5751","DOI":"10.1128\/MCB.00415-09","article-title":"Parathyroid Hormone-Related Peptide Represses Chondrocyte Hypertrophy through a Protein Phosphatase 2A\/Histone Deacetylase 4\/MEF2 Pathway","volume":"29","author":"Kozhemyakina","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.devcel.2010.09.008","article-title":"Zfp521 Is a Target Gene and Key Effector of Parathyroid Hormone-Related Peptide Signaling in Growth Plate Chondrocytes","volume":"19","author":"Correa","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1128\/MCB.20.11.4149-4158.2000","article-title":"Phosphorylation of SOX9 by Cyclic AMP-Dependent Protein Kinase A Enhances SOX9\u2019s Ability To Transactivate ACol2a1 Chondrocyte-Specific Enhancer","volume":"20","author":"Huang","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1101\/gad.990702","article-title":"FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease","volume":"16","author":"Ornitz","year":"2002","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0092-8674(00)81069-7","article-title":"Fibroblast Growth Factor Receptor 3 Is a Negative Regulator of Bone Growth","volume":"84","author":"Deng","year":"1996","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ng0496-390","article-title":"Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3","volume":"12","author":"Colvin","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1086\/508433","article-title":"A Novel Mutation in FGFR3 Causes Camptodactyly, Tall Stature, and Hearing Loss (CATSHL) Syndrome","volume":"79","author":"Toydemir","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1242\/dev.125.24.4977","article-title":"Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3","volume":"125","author":"Naski","year":"1998","journal-title":"Development"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1101\/gad.13.11.1361","article-title":"FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway","volume":"13","author":"Sahni","year":"1999","journal-title":"Genes Dev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.devcel.2007.09.016","article-title":"Snail1 Is a Transcriptional Effector of FGFR3 Signaling during Chondrogenesis and Achondroplasias","volume":"13","author":"Vega","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.yexcr.2004.03.011","article-title":"FGF2 inhibits proliferation and alters the cartilage-like phenotype of RCS cells","volume":"297","author":"Krejci","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1083\/jcb.200205025","article-title":"FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest","volume":"158","author":"Laplantine","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1534-5807(02)00261-7","article-title":"Interaction of FGF, Ihh\/Pthlh, and BMP Signaling Integrates Chondrocyte Proliferation and Hypertrophic Differentiation","volume":"3","author":"Minina","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1083\/jcb.200302075","article-title":"A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation","volume":"161","author":"Dailey","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1750-1172-8-71","article-title":"Assessment of bone mineral density by dual energy x-ray absorptiometry in patients with mucopolysaccharidoses","volume":"8","author":"Lin","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jocd.2013.03.004","article-title":"Low Bone Mineral Content and Challenges in Interpretation of Dual-Energy X-Ray Absorptiometry in Children with Mucopolysaccharidosis Types I, II, and VI","volume":"17","author":"Polgreen","year":"2014","journal-title":"J. Clin. Densitom."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/00003086-199108000-00041","article-title":"Hurler syndrome with special reference to histologic abnormalities of the growth plate","volume":"269","author":"Silveri","year":"1991","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/hmg\/6.4.503","article-title":"Murine Mucopolysaccharidosis Type I: Targeted Disruption of the Murine \u03b1-L-Iduronidase Gene","volume":"6","author":"Clarke","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1203\/00006450-197911000-00018","article-title":"Alpha-L-iduronidase Deficiency in a Cat: A Model of Mucopolysaccharidosis I","volume":"13","author":"Haskins","year":"1979","journal-title":"Pediatr. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ymgme.2008.07.003","article-title":"Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy","volume":"95","author":"Herati","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6558","DOI":"10.1038\/s41598-020-63451-4","article-title":"Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog","volume":"10","author":"Mansour","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10545-012-9522-x","article-title":"Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII","volume":"36","author":"Rowan","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1172\/JCI116268","article-title":"Arylsulfatase B-deficient mucopolysaccharidosis in rats","volume":"91","author":"Yoshida","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2460\/javma.2004.224.553","article-title":"Mucopolysaccharidosis type VII in a German Shepherd Dog","volume":"224","author":"Dombrowski","year":"2004","journal-title":"J. Am. Veter. Med. Assoc."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bone.2013.03.014","article-title":"Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs","volume":"55","author":"Chiaro","year":"2013","journal-title":"Bone"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.ymgme.2021.06.005","article-title":"Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity","volume":"133","author":"Peck","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_123","first-page":"7075","article-title":"Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I","volume":"24","author":"Kuehn","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1399-0004.1998.tb02745.x","article-title":"Murine MPS I: Insights into the pathogenesis of Hurler syndrome","volume":"53","author":"Russell","year":"1998","journal-title":"Clin. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.bone.2016.01.029","article-title":"Altered interaction and distribution of glycosaminoglycans and growth factors in mucopolysaccharidosis type I bone disease","volume":"88","author":"Kingma","year":"2016","journal-title":"Bone"},{"key":"ref_126","first-page":"677","article-title":"Long-term effects of bone marrow transplantation in dogs with mucopolysaccharidosis I","volume":"134","author":"Breider","year":"1989","journal-title":"Am. J. Pathol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1097\/00005072-198311000-00006","article-title":"Meningiomas in Young Cats with Mucopolysaccharidosis I","volume":"42","author":"Haskins","year":"1983","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Frohbergh, M., Ge, Y., Meng, F., Karabul, N., Solyom, A., Lai, A., Iatridis, J., Schuchman, E.H., and Simonaro, C.M. (2014). Dose Responsive Effects of Subcutaneous Pentosan Polysulfate Injection in Mucopolysaccharidosis Type VI Rats and Comparison to Oral Treatment. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100882"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"115195","DOI":"10.1016\/j.bone.2019.115195","article-title":"Cell cycle progression is disrupted in murine MPS VII growth plate leading to reduced chondrocyte proliferation and transition to hypertrophy","volume":"132","author":"Jiang","year":"2020","journal-title":"Bone"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.chembiol.2004.11.020","article-title":"Structural Insights into Biological Roles of Protein-Glycosaminoglycan Interactions","volume":"12","author":"Raman","year":"2005","journal-title":"Chem. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1146\/annurev.biochem.68.1.729","article-title":"Functions of Cell Surface Heparan Sulfate Proteoglycans","volume":"68","author":"Bernfield","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1073\/pnas.0437842100","article-title":"Structural specificity of heparin binding in the fibroblast growth factor family of proteins","volume":"100","author":"Raman","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1182\/blood-2005-02-0657","article-title":"Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells","volume":"106","author":"Pan","year":"2005","journal-title":"Blood"},{"key":"ref_134","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_135","doi-asserted-by":"crossref","first-page":"C1387","DOI":"10.1152\/ajpcell.00346.2007","article-title":"Endogenous heparan sulfate and heparin modulate bone morphogenetic protein-4 signaling and activity","volume":"294","author":"Khan","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_136","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 \u03b1-l-iduronidase","volume":"286","author":"Holley","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ymgme.2009.03.005","article-title":"Mechanism of shortened bones in mucopolysaccharidosis VII","volume":"97","author":"Metcalf","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ymgme.2018.04.014","article-title":"Delayed development of ossification centers in the tibia of prenatal and early postnatal MPS VII mice","volume":"124","author":"Jiang","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ymgme.2015.09.008","article-title":"Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs","volume":"116","author":"Peck","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"115042","DOI":"10.1016\/j.bone.2019.115042","article-title":"Molecular profiling of failed endochondral ossification in mucopolysaccharidosis VII","volume":"128","author":"Peck","year":"2019","journal-title":"Bone"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1128\/MCB.19.6.4431","article-title":"Collagenase 3 Is a Target of Cbfa1, a Transcription Factor of the runt Gene Family Involved in Bone Formation","volume":"19","author":"Alvarez","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.2353\/ajpath.2009.090211","article-title":"Glycosaminoglycan-Mediated Loss of Cathepsin K Collagenolytic Activity in MPS I Contributes to Osteoclast and Growth Plate Abnormalities","volume":"175","author":"Wilson","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_143","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_144","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1182\/blood-2014-11-608075","article-title":"Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: An international multicenter study","volume":"125","author":"Aldenhoven","year":"2015","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1053\/j.seminhematol.2009.10.008","article-title":"Transplant Outcomes in Mucopolysaccharidoses","volume":"47","author":"Prasad","year":"2010","journal-title":"Semin. Hematol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.wneu.2020.04.055","article-title":"Treatment of Severe Kyphoscoliosis in Children with Mucopolysaccharidosis Type I (Pfaundler\u2013Hurler Syndrome) Using the Growing Rod Technique: A Case Series with Mid-Term Results","volume":"139","author":"Hofmann","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1111\/j.1365-2044.1994.tb04360.x","article-title":"Anaesthesia and mucopolysaccharidoses: A Review of Airway Problems in Children","volume":"49","author":"Walker","year":"1994","journal-title":"Anaesthesia"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.17305\/bjbms.2017.2201","article-title":"Anesthesia for patients with mucopolysaccharidoses: Comprehensive review of the literature with emphasis on airway management","volume":"18","author":"Clark","year":"2018","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/2408402","article-title":"Mucopolysaccharidoses I and II: Brief Review of Therapeutic Options and Supportive\/Palliative Therapies","volume":"2020","author":"Nan","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_150","first-page":"277","article-title":"The efficacy of Schroth`s 3-dimensional exercise therapy in the treatment of adolescent idiopathic scoliosis in Turkey","volume":"10","author":"Otman","year":"2005","journal-title":"Neurosciences"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3109\/09593985.2010.533342","article-title":"Physical exercises in the treatment of adolescent idiopathic scoliosis: An updated systematic review","volume":"27","author":"Fusco","year":"2011","journal-title":"Physiother. Theory Pract."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.sbspro.2013.04.195","article-title":"Early Physical Therapy Intervention in Infant Hip Dysplasia","volume":"76","author":"Marinela","year":"2013","journal-title":"Procedia-Soc. Behav. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1182\/blood-2012-09-455238","article-title":"Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning","volume":"121","author":"Boelens","year":"2013","journal-title":"Blood"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.bbmt.2015.02.011","article-title":"Hematopoietic Cell Transplantation for Mucopolysaccharidosis Patients Is Safe and Effective: Results after Implementation of International Guidelines","volume":"21","author":"Aldenhoven","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e07740","DOI":"10.1016\/j.heliyon.2021.e07740","article-title":"Long-term evolution of mucopolysaccharidosis type I in twins treated with enzyme replacement therapy plus hematopoietic stem cells transplantation","volume":"7","author":"Rosales","year":"2021","journal-title":"Heliyon"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1056\/NEJMoa032613","article-title":"Cord-Blood Transplants from Unrelated Donors in Patients with Hurler\u2019s Syndrome","volume":"350","author":"Staba","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_157","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_158","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/sj.bmt.1704105","article-title":"Outcome of 27 patients with Hurler\u2019s syndrome transplanted from either related or unrelated haematopoietic stem cell sources","volume":"31","author":"Souillet","year":"2003","journal-title":"Bone Marrow Transplant."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/8904_2015_521","article-title":"Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation","volume":"Volume 29","author":"Morava","year":"2015","journal-title":"JIMD Reports"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/8904_2014_395","article-title":"Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation","volume":"Volume 20","author":"Zschocke","year":"2014","journal-title":"JIMD Reports"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ymgme.2012.07.016","article-title":"An exploratory study of brain function and structure in mucopolysaccharidosis type I: Long term observations following hematopoietic cell transplantation (HCT)","volume":"107","author":"Shapiro","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/ana.24246","article-title":"Early treatment is associated with improved cognition in Hurler syndrome: Early UCBT in MPS1","volume":"76","author":"Poe","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1136\/adc.76.2.92","article-title":"Bone marrow transplantation for mucopolysaccharidosis type I: Experience of two British centres","volume":"76","author":"Vellodi","year":"1997","journal-title":"Arch. Dis. Child."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ymgmr.2014.12.006","article-title":"Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: Clinical, biochemical, and pathological improvements","volume":"2","author":"Yasuda","year":"2015","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.jpeds.2012.07.052","article-title":"Enzyme Replacement is Associated with Better Cognitive Outcomes after Transplant in Hurler Syndrome","volume":"162","author":"Eisengart","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1302\/0301-620X.76B6.7983131","article-title":"Bone-Marrow Transplantation in Hurler\u2019s Syndrome. Effect on Skeletal Development","volume":"76","author":"Field","year":"1994","journal-title":"J. Bone Joint Surg. Br."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2106\/JBJS.O.00601","article-title":"Progression of Hip Dysplasia in Mucopolysaccharidosis Type I Hurler After Successful Hematopoietic Stem Cell Transplantation","volume":"98","author":"Langereis","year":"2016","journal-title":"J. Bone Jt. Surg."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/01241398-200401000-00019","article-title":"Musculoskeletal Manifestations of Hurler Syndrome","volume":"24","author":"Weisstein","year":"2004","journal-title":"J. Pediatr. Orthop."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-016-0470-7","article-title":"Musculoskeletal manifestations in mucopolysaccharidosis type I (Hurler syndrome) following hematopoietic stem cell transplantation","volume":"11","author":"Schmidt","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/01241398-199903000-00026","article-title":"Genu Valgum Deformity in Hurler Syndrome After Hematopoietic Stem Cell Transplantation: Correction by Surgical Intervention","volume":"19","author":"Odunusi","year":"1999","journal-title":"J. Pediatr. Orthop."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/BPO.0000000000000464","article-title":"Lower Extremity Deformity Management in MPS IVA, Morquio-Brailsford Syndrome: Preliminary Report of Hemiepiphysiodesis Correction of Genu Valgum","volume":"36","author":"Cooper","year":"2016","journal-title":"J. Pediatr. Orthop."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13052-018-0557-y","article-title":"Orthopaedic challenges for mucopolysaccharidoses","volume":"44","author":"Borgo","year":"2018","journal-title":"Ital. J. Pediatr."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-3-662-44587-7","article-title":"Perioperative Medullary Complications in Spinal and Extra-Spinal Surgery in Mucopolysaccharidosis: A Case Series of Three Patients","volume":"Volume 16","author":"Zschocke","year":"2014","journal-title":"JIMD Reports"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"100787","DOI":"10.1016\/j.ymgmr.2021.100787","article-title":"\u201cGrowth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients\u201d","volume":"28","author":"Cattoni","year":"2021","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ymgme.2013.11.013","article-title":"Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1\u20132years in children with Hurler or Hunter syndrome","volume":"111","author":"Polgreen","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/sj.bmt.1704481","article-title":"Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood","volume":"33","author":"Bakker","year":"2004","journal-title":"Bone Marrow Transplant."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1182\/blood.V86.2.825.bloodjournal862825","article-title":"Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone","volume":"86","author":"Giorgiani","year":"1995","journal-title":"Blood"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13052-019-0691-1","article-title":"The use of recombinant human growth hormone in patients with Mucopolysaccharidoses and growth hormone deficiency: A case series","volume":"45","author":"Cattoni","year":"2019","journal-title":"Ital. J. Pediatr."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/jmd2.12291","article-title":"Predictors of growth patterns in children with mucopolysaccharidosis I after haematopoietic stem cell transplantation","volume":"63","author":"Maier","year":"2022","journal-title":"JIMD Rep."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10545-010-9262-8","article-title":"Growth, final height and endocrine sequelae in a UK population of patients with Hurler syndrome (MPS1H)","volume":"34","author":"Gardner","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1542\/peds.2007-3847","article-title":"Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I","volume":"123","author":"Clarke","year":"2009","journal-title":"Pediatrics"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1056\/NEJM200101183440304","article-title":"Enzyme-Replacement Therapy in Mucopolysaccharidosis I","volume":"344","author":"Kakkis","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"60ra89","DOI":"10.1126\/scitranslmed.3001380","article-title":"Replacing the Enzyme \u03b1- 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_184","doi-asserted-by":"crossref","unstructured":"Gabrielli, O., Clarke, L.A., Ficcadenti, A., Santoro, L., Zampini, L., Volpi, N., and Coppa, G.V. (2016). 12 year follow up of enzyme-replacement therapy in two siblings with attenuated mucopolysaccharidosis I: The important role of early treatment. BMC Med. Genet., 17.","DOI":"10.1186\/s12881-016-0284-4"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13023-015-0344-4","article-title":"Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: A retrospective case series analysis of nine sibships","volume":"10","author":"Bay","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.jpeds.2004.01.046","article-title":"Enzyme replacement therapy for mucopolysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human \u03b1-L-iduronidase (laronidase)","volume":"144","author":"Wraith","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1001\/archopht.125.10.1353","article-title":"Ocular Changes in Patients with Mucopolysaccharidosis I Receiving Enzyme Replacement Therapy: A 4-Year Experience","volume":"125","author":"Pitz","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jpeds.2016.08.033","article-title":"Outcomes of Long-Term Treatment with Laronidase in Patients with Mucopolysaccharidosis Type I","volume":"178","author":"Laraway","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10545-010-9059-9","article-title":"Efficacy of recombinant human \u03b1-L-iduronidase (laronidase) on restricted range of motion of upper extremities in mucopolysaccharidosis type I patients","volume":"33","author":"Marucha","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymgme.2006.08.007","article-title":"A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years","volume":"90","author":"Sifuentes","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s00431-011-1644-x","article-title":"Diagnosis and treatment trends in mucopolysaccharidosis I: Findings from the MPS I Registry","volume":"171","author":"Underhill","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4238\/gmr.15017850","article-title":"Short Communication Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: Results of a long-term follow-up of Brazilian siblings","volume":"15","author":"Franco","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/j.1399-0004.2009.01324.x","article-title":"Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age\u2013A sibling control study","volume":"77","author":"McGill","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ymgme.2013.03.005","article-title":"Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice","volume":"109","author":"Baldo","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1021\/mp200136x","article-title":"Reversal of Lysosomal Storage in Brain of Adult MPS-I Mice with Intravenous Trojan Horse-Iduronidase Fusion Protein","volume":"8","author":"Boado","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13023-018-0849-8","article-title":"Neurocognitive and somatic stabilization in pediatric patients with severe Mucopolysaccharidosis Type I after 52 weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein (valanafusp alpha): An open label phase 1-2 trial","volume":"13","author":"Giugliani","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/01.GIM.0000154299.22120.6A","article-title":"Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome","volume":"7","author":"Grewal","year":"2005","journal-title":"Genet. Med."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ymgme.2016.01.011","article-title":"Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10year combined experience of 2 centres","volume":"117","author":"Ghosh","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e1242","DOI":"10.1542\/peds.2009-2843","article-title":"Laronidase for Cardiopulmonary Disease in Hurler Syndrome 12 Years After Bone Marrow Transplantation","volume":"126","author":"Valayannopoulos","year":"2010","journal-title":"Pediatrics"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/sj.bmt.1705934","article-title":"Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome","volume":"41","author":"Tolar","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Kubaski, F., de Oliveira Poswar, F., Michelin-Tirelli, K., Matte, U.D.S., Horovitz, D.D., Barth, A.L., Baldo, G., Vairo, F., and Giugliani, R. (2020). Mucopolysaccharidosis Type I. Diagnostics, 10.","DOI":"10.3390\/diagnostics10030161"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3324\/haematol.2011.058644","article-title":"Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler\u2019s syndrome after pharmacological enzyme replacement therapy","volume":"97","author":"Saif","year":"2012","journal-title":"Haematologica"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"E96","DOI":"10.1111\/petr.12231","article-title":"Hematopoietic stem cell transplantation effects on spinal cord compression in Hurler","volume":"18","author":"Ferrara","year":"2014","journal-title":"Pediatr. Transplant."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13023-015-0255-4","article-title":"Sleep disordered breathing in mucopolysaccharidosis I: A multivariate analysis of patient, therapeutic and metabolic correlators modifying long term clinical outcome","volume":"10","author":"Pal","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_205","first-page":"iii","article-title":"A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry\u2019s disease and mucopolysaccharidosis type 1","volume":"10","author":"Connock","year":"2006","journal-title":"Health Technol. Assess."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/sj.mt.6300112","article-title":"Improvements in Mucopolysaccharidosis I Mice After Adult Retroviral Vector\u2013mediated Gene Therapy with Immunomodulation","volume":"15","author":"Ma","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.ymthe.2004.10.006","article-title":"Neonatal Gene Therapy of MPS I Mice by Intravenous Injection of a Lentiviral Vector","volume":"11","author":"Kobayashi","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2004.01.015","article-title":"Neonatal retroviral vector-mediated hepatic gene therapy reduces bone, joint, and cartilage disease in mucopolysaccharidosis VII mice and dogs","volume":"82","author":"Mango","year":"2004","journal-title":"Mol. Genet. Metab."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ymthe.2004.03.011","article-title":"Correction of metabolic, craniofacial, and neurologic abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human \u03b1-l-iduronidase gene","volume":"9","author":"Hartung","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41390-018-0095-8","article-title":"Tailoring the AAV2 capsid vector for bone-targeting","volume":"84","author":"Barrera","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/nm0797-771","article-title":"Decreased Lysosomal Storage in the Adult MPS VII Mouse Brain in the Vicinity of Grafts of Retroviral Vector-Corrected Fibroblasts Secreting High Levels of B-Glucuronidase","volume":"3","author":"Taylor","year":"1997","journal-title":"Nat. Med."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/sj.gt.3300504","article-title":"Retrovirus-mediated transfer of the human \u03b1- L-iduronidase cDNA into human hematopoietic progenitor cells leads to correction in trans of Hurler fibroblasts","volume":"4","author":"Huang","year":"1997","journal-title":"Gene Ther."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1182\/blood.V99.5.1857","article-title":"Retrovirally mediated correction of bone marrow\u2013derived mesenchymal stem cells from patients with mucopolysaccharidosis type I","volume":"99","author":"Baxter","year":"2002","journal-title":"Blood"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1089\/hum.2006.17.1112","article-title":"Limited Transgene Immune Response and Long-Term Expression of Human\u03b1-L-Iduronidase in Young Adult Mice with Mucopolysaccharidosis Type I by Liver-Directed Gene Therapy","volume":"17","author":"Reyero","year":"2006","journal-title":"Hum. Gene Ther."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/sj.mt.6300201","article-title":"Correction of Clinical Manifestations of Canine Mucopolysaccharidosis I with Neonatal Retroviral Vector Gene Therapy","volume":"15","author":"Traas","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1089\/hum.2005.16.81","article-title":"Gene Therapy for a Mucopolysaccharidosis Type I Murine Model with Lentiviral-IDUA Vector","volume":"16","author":"Villani","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/s41591-018-0195-3","article-title":"Dynamics of genetically engineered hematopoietic stem and progenitor cells after autologous transplantation in humans","volume":"24","author":"Scala","year":"2018","journal-title":"Nat. Med."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1096-7192(03)00116-1","article-title":"Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow","volume":"79","author":"Zheng","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"19958","DOI":"10.1073\/pnas.0908528106","article-title":"Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome","volume":"106","author":"Wang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1182\/blood-2010-04-278234","article-title":"Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model","volume":"116","author":"Visigalli","year":"2010","journal-title":"Blood"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1089\/hum.2016.068","article-title":"Preclinical Testing of the Safety and Tolerability of LV-Mediated above Normal Alpha-L-Iduronidase Expression in Murine and Human Hematopoietic Cells Using Toxicology and Biodistribution GLP Studies","volume":"27","author":"Visigalli","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa2106596","article-title":"Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome","volume":"385","author":"Gentner","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/nm1095-1017","article-title":"Engraftment of gene\u2013modified umbilical cord blood cells in neonates with adenosine deaminase deficiency","volume":"1","author":"Kohn","year":"1995","journal-title":"Nat. Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev-biochem-060713-035418","article-title":"Genome Engineering with Targetable Nucleases","volume":"83","author":"Carroll","year":"2014","journal-title":"Annu. Rev. Biochem."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jconrel.2018.08.031","article-title":"In vivo genome editing of mucopolysaccharidosis I mice using the CRISPR\/Cas9 system","volume":"288","author":"Schuh","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1038\/s41467-019-11962-8","article-title":"Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I","volume":"10","author":"Scharenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_227","first-page":"S68","article-title":"EMPOWERS: A phase 1\/2 clinical trial of SB-318 ZFN-mediated in vivo human genome editing for treatment of MPS I (Hurler syndrome)","volume":"126","author":"Harmatz","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/mt.2009.87","article-title":"Systemic Correction of Storage Disease in MPS I NOD\/SCID Mice Using the Sleeping Beauty Transposon System","volume":"17","author":"Aronovich","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"pdb-top095513","DOI":"10.1101\/pdb.top095513","article-title":"Introducing Genes into Mammalian Cells: Viral Vectors","volume":"2020","author":"Gao","year":"2020","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1172\/JCI37630","article-title":"The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy","volume":"119","author":"Montini","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-006-0280-4","article-title":"New therapeutic options for lysosomal storage disorders: Enzyme replacement, small molecules and gene therapy","volume":"121","author":"Beck","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.2174\/138920111798376932","article-title":"Substrate reduction therapies for mucopolysaccharidoses","volume":"12","author":"Piotrowska","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_233","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_234","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_235","doi-asserted-by":"crossref","first-page":"CR196","DOI":"10.12659\/MSM.881715","article-title":"Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: Assessment of effects on cognitive functions and general status of patients","volume":"17","author":"Piotrowska","year":"2011","journal-title":"Med Sci. Monit."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-3-662-47467-9","article-title":"Adverse Effects of Genistein in a Mucopolysaccharidosis Type I Mouse Model","volume":"Volume 23","author":"Zschocke","year":"2015","journal-title":"JIMD Reports"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ymgme.2016.04.002","article-title":"N-butyldeoxynojirimycin treatment restores the innate fear response and improves learning in mucopolysaccharidosis IIIA mice","volume":"118","author":"Kaidonis","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ejhg.2009.143","article-title":"Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses","volume":"18","author":"Kaidonis","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Keeling, K.M., Wang, D., Dai, Y., Murugesan, S., Chenna, B., Clark, J., Belakhov, V., Kandasamy, J., Velu, S.E., and Baasov, T. (2013). Attenuation of Nonsense-Mediated mRNA Decay Enhances In vivo Nonsense Suppression. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060478"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ymgme.2013.12.007","article-title":"Long-term nonsense suppression therapy moderates MPS I-H disease progression","volume":"111","author":"Gunn","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1089\/adt.2011.0370","article-title":"Identification and Characterization of Pharmacological Chaperones to Correct Enzyme Deficiencies in Lysosomal Storage Disorders","volume":"9","author":"Valenzano","year":"2011","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_242","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_243","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.devcel.2011.07.016","article-title":"Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular Clearance","volume":"21","author":"Medina","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13023-021-01805-5","article-title":"The multi-domain responder index: A novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases","volume":"16","author":"Tandon","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_245","unstructured":"(2022, September 16). Available online: https:\/\/Clinicaltrials.Gov\/Ct2\/Show\/Results\/NCT00146757?View=results."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/gim.2014.25","article-title":"The natural history of MPS I: Global perspectives from the MPS I Registry","volume":"16","author":"Beck","year":"2014","journal-title":"Genet. Med."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1177\/0003489414550154","article-title":"Airway-related symptoms and surgeries in patients with mucopolysaccharidosis I","volume":"124","author":"Arn","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_248","unstructured":"(2022, September 16). Available online: https:\/\/Clinicaltrials.Gov\/Ct2\/Show\/Results\/NCT00144781?Cond=NCT00144781&draw=2&rank=1."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"108","DOI":"10.12891\/ceog1845.2015","article-title":"Successful pregnancy and breastfeeding in a woman with mucopolysaccharidosis type I while receiving laronidase enzyme replacement therapy","volume":"42","author":"Castorina","year":"2015","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_250","unstructured":"(2022, September 16). Available online: https:\/\/Clinicaltrials.Gov\/Ct2\/Show\/Results\/NCT01173016?Cond=NCT01173016&draw=2&rank=1."},{"key":"ref_251","unstructured":"(2022, September 16). Available online: https:\/\/Clinicaltrials.Gov\/Ct2\/Show\/Results\/NCT02437253?Cond=NCT02437253&draw=2&rank=1."},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Simonaro, C.M., Tomatsu, S., Sikora, T., Kubaski, F., Frohbergh, M., Guevara, J.M., Wang, R.Y., Vera, M., Kang, J.L., and Smith, L.J. (2016). Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153136"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s10545-016-9974-5","article-title":"Treatment with pentosan polysulphate in patients with MPS I: Results from an open label, randomized, monocentric phase II study","volume":"39","author":"Hennermann","year":"2016","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Eliyahu, E., Wolfson, T., Ge, Y., Jepsen, K.J., Schuchman, E.H., and Simonaro, C.M. (2011). Anti-TNF-Alpha Therapy Enhances the Effects of Enzyme Replacement Therapy in Rats with Mucopolysaccharidosis Type VI. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022447"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"bqaa008","DOI":"10.1210\/endocr\/bqaa008","article-title":"C-Type Natriuretic Peptide Restores Growth Impairment Under Enzyme Replacement in Mice with Mucopolysaccharidosis VII","volume":"161","author":"Yamashita","year":"2020","journal-title":"Endocrinology"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1172\/JCI94130","article-title":"mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy","volume":"127","author":"Bartolomeo","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.3727\/096368912X636894","article-title":"Intracerebroventricular Transplantation of Human Bone Marrow-Derived Multipotent Progenitor Cells in an Immunodeficient Mouse Model of Mucopolysaccharidosis Type I (MPS-I)","volume":"21","author":"Nan","year":"2012","journal-title":"Cell Transplant."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1634\/stemcells.2008-0008","article-title":"Lentiviral-Transduced Human Mesenchymal Stem Cells Persistently Express Therapeutic Levels of Enzyme in a Xenotransplantation Model of Human Disease","volume":"26","author":"Meyerrose","year":"2008","journal-title":"Stem Cells"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/sj.bmt.1703650","article-title":"Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)","volume":"30","author":"Day","year":"2002","journal-title":"Bone Marrow Transplant."},{"key":"ref_260","doi-asserted-by":"crossref","unstructured":"Iolascon, G., and Moretti, A. (2022). The Rationale for Using Neridronate in Musculoskeletal Disorders: From Metabolic Bone Diseases to Musculoskeletal Pain. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23136921"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/891596","article-title":"Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic Phenotype","volume":"2013","author":"Tummolo","year":"2013","journal-title":"Case Rep. Med."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ymgme.2009.07.015","article-title":"Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II","volume":"98","author":"Wang","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s10545-016-0006-2","article-title":"Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: The 30-year University of Minnesota experience","volume":"40","author":"Rodgers","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ymgme.2014.05.013","article-title":"Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?","volume":"114","author":"Tomatsu","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"9473","DOI":"10.1038\/s41598-017-09958-9","article-title":"Neonatal umbilical cord blood transplantation halts skeletal disease progression in the murine model of MPS-I","volume":"7","author":"Azario","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1182\/blood-2014-06-581207","article-title":"Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I","volume":"125","author":"Pievani","year":"2015","journal-title":"Blood"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ymgme.2020.05.001","article-title":"Neonatal combination therapy improves some of the clinical manifestations in the Mucopolysaccharidosis type I murine model","volume":"130","author":"Santi","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/mt.2015.99","article-title":"Neonatal Systemic AAV Induces Tolerance to CNS Gene Therapy in MPS I Dogs and Nonhuman Primates","volume":"23","author":"Hinderer","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/jnr.10764","article-title":"Brain transplantation of genetically engineered human neural stem cells globally corrects brain lesions in the mucopolysaccharidosis type VII mouse","volume":"74","author":"Meng","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1038\/s41467-021-24443-8","article-title":"In utero adenine base editing corrects multi-organ pathology in a lethal lysosomal storage disease","volume":"12","author":"Bose","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1182\/blood.V97.6.1625","article-title":"In utero transplantation of fetal liver cells in the mucopolysaccharidosis type VII mouse results in low-level chimerism, but overexpression of \u03b2-glucuronidase can delay onset of clinical signs","volume":"97","author":"Casal","year":"2001","journal-title":"Blood"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1006\/bcmd.2001.0453","article-title":"In Utero Fetal Liver Cell Transplantation without Toxic Irradiation Alleviates Lysosomal Storage in Mice with Mucopolysaccharidosis Type VII","volume":"27","author":"Barker","year":"2001","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13023-017-0662-9","article-title":"Open issues in Mucopolysaccharidosis type I-Hurler","volume":"12","author":"Parini","year":"2017","journal-title":"Orphanet J. Rare Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:37:43Z","timestamp":1760143063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":273,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911168"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911168","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]}}}