{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:29:49Z","timestamp":1786681789594,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceuticals U.S.A., Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Neonatal Screen.","IJNS"],"abstract":"<jats:p>Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome), is a rare X-linked lysosomal disease that leads to progressive tissue and organ damage. Early treatment is essential as most symptoms of MPS II are not reversible. Consequently, MPS II has been added to many newborn screening (NBS) programs. This narrative literature review provides practical recommendations from a multidisciplinary expert panel on the US-based NBS for MPS II and its diagnosis and clinical management. Recommendations for NBS programs include aiming for universal access to NBS within their jurisdiction, implementing tiered testing to support diagnostic accuracy, and providing infrastructure for confirmatory testing and post-screening support for families. Recommendations for health care providers (HCPs) include communicating test results empathetically and alongside verbal and written information, allowing families to express their feelings, and consulting an MPS II specialist to support treatment recommendations. The NBS programs and HCPs should work together to ensure positive screening results are communicated effectively and to provide equitable access to treatment and long-term care. Such a coordinated and appropriately resourced effort involving NBS programs, HCPs, and patient advocates will ensure better support for families and the best possible outcomes for individuals with MPS II.<\/jats:p>","DOI":"10.3390\/ijns12030066","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:45:06Z","timestamp":1786545906000},"page":"66","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucopolysaccharidosis Type II Screening, Diagnosis, and Management: A Literature Review and Practical Recommendations for Newborn Screening Programs and Health Care Providers to Support Families and Improve Outcomes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-3820","authenticated-orcid":false,"given":"Amy","family":"Gaviglio","sequence":"first","affiliation":[{"name":"Connetics Consulting LLC, Minneapolis, MN 55417, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3841-9064","authenticated-orcid":false,"given":"Natasha","family":"Bonhomme","sequence":"additional","affiliation":[{"name":"Expecting Health, Washington, DC 20016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Burton","sequence":"additional","affiliation":[{"name":"Edwards Family Division of Genetics and Rare Diseases at Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-5052","authenticated-orcid":false,"given":"Norman Matthew","family":"Ellinwood","sequence":"additional","affiliation":[{"name":"National MPS Society, Durham, NC 27709-4686, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Muenzer","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9681-6271","authenticated-orcid":false,"given":"Kim","family":"Stephens","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Pathak","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc., Lexington, MA 02421, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4920-7627","authenticated-orcid":false,"given":"Carolyn","family":"Schaeffer-Koziol","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals USA, Inc., Lexington, MA 02421, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bilyeu, H., Washburn, J., Vermette, L., and Klug, T. (2020). Validation and Implementation of a Highly Sensitive and Efficient Newborn Screening Assay for Mucopolysaccharidosis Type II. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6040079"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107557","DOI":"10.1016\/j.ymgme.2023.107557","article-title":"Newborn Screening for Mucopolysaccharidosis Type II: Lessons Learned","volume":"140","author":"Burton","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_3","first-page":"107","article-title":"Mucopolysaccharidosis Type II, Hunter\u2019s Syndrome","volume":"12","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13023-021-01880-8","article-title":"Epidemiology of Mucopolysaccharidoses (MPS) in United States: Challenges and Opportunities","volume":"16","author":"Puckett","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_5","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_6","first-page":"101005","article-title":"Clinical Characteristics and Somatic Burden of Patients with Mucopolysaccharidosis II with or Without Neurological Involvement: An Analysis from the Hunter Outcome Survey","volume":"37","author":"Lau","year":"2023","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/BF00691155","article-title":"Morphological Observations in the Nervous System of Prenatal Mucopolysaccharidosis II (M. Hunter)","volume":"48","author":"Meier","year":"1979","journal-title":"Acta Neuropathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1750-1172-6-72","article-title":"Mucopolysaccharidosis Type II: European Recommendations for the Diagnosis and Multidisciplinary Management of a Rare Disease","volume":"6","author":"Scarpa","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41436-020-0909-z","article-title":"Treatment of Mucopolysaccharidosis Type II (Hunter Syndrome): A Delphi Derived Practice Resource of the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"McBride","year":"2020","journal-title":"Genet. Med."},{"key":"ref_11","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. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1136\/adc.57.11.828","article-title":"Mild Form of Hunter\u2019s Syndrome: Clinical Delineation Based on 31 Cases","volume":"57","author":"Young","year":"1982","journal-title":"Arch. Dis. Child."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1469-8749.1983.tb13794.x","article-title":"The Natural History of the Severe Form of Hunter\u2019s Syndrome: A Study Based on 52 Cases","volume":"25","author":"Young","year":"1983","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1007\/s10545-009-1119-7","article-title":"Mortality and Cause of Death in Mucopolysaccharidosis Type II-A Historical Review Based on Data from the Hunter Outcome Survey (HOS)","volume":"32","author":"Jones","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00431-012-1703-y","article-title":"Diagnosing Hunter Syndrome in Pediatric Practice: Practical Considerations and Common Pitfalls","volume":"171","author":"Burton","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_16","first-page":"100845","article-title":"Timing is Everything: Clinical Courses of Hunter Syndrome Associated with Age at Initiation of Therapy in a Sibling Pair","volume":"30","author":"Grant","year":"2022","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"100330","DOI":"10.1016\/j.gim.2022.10.012","article-title":"Evidence and Recommendation for Mucopolysaccharidosis Type II Newborn Screening in the United States","volume":"25","author":"Ream","year":"2023","journal-title":"Genet. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1S","DOI":"10.1097\/01.gim.0000223891.82390.ad","article-title":"Newborn Screening: Toward a Uniform Screening Panel and System","volume":"8","author":"Watson","year":"2006","journal-title":"Genet. Med."},{"key":"ref_20","unstructured":"Wilson, J.M.G., and Jungner, G. (1968). Principles and Practive of Screening for Disease, World Health Organization."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2471\/BLT.07.050112","article-title":"Revisiting Wilson and Jungner in the Genomic Age: A Review of Screening Criteria over the Past 40 Years","volume":"86","author":"Andermann","year":"2008","journal-title":"Bull. World Health Organ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E422","DOI":"10.1503\/cmaj.171154","article-title":"Consolidated Principles for Screening Based on a Systematic Review and Consensus Process","volume":"190","author":"Dobrow","year":"2018","journal-title":"Can. Med. Assoc. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1891\/0739-6686.29.113","article-title":"Newborn Screening: Ethical, Legal, and Social Implications","volume":"29","author":"Anderson","year":"2011","journal-title":"Annu. Rev. Nurs. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Currier, R.J. (2022). Newborn Screening is on a Collision Course with Public Health Ethics. Int. J. Neonatal Screen., 8.","DOI":"10.3390\/ijns8040051"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lietsch, M., Chan, K., Taylor, J., Lee, B.H., Ciafaloni, E., Kwon, J.M., Waldrop, M.A., Butterfield, R.J., Rathore, G., and Veerapandiyan, A. (2024). Long-Term Follow-Up Cares and Check Initiative: A Program to Advance Long-Term Follow-Up in Newborns Identified with a Disease Through Newborn Screening. Int. J. Neonatal Screen., 10.","DOI":"10.3390\/ijns10020034"},{"key":"ref_26","unstructured":"Dylan, S., Geer, L., Beckhardt, S., Bonhomme, N., Brower, A., Donigan, K., Frisk, S., Harrison, C., Illes, J., and Mayer, C. (2025, September 30). Pioneering the New Era of Newborn Screening. Available online: https:\/\/everylifefoundation.org\/wp-content\/uploads\/2023\/09\/ELF-NBS-WhitePaper_Final.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1001\/jamapediatrics.2014.2465","article-title":"Universal State Newborn Screening Programs Can Reduce Health Disparities","volume":"169","author":"Brosco","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Odenwald, B., Brockow, I., Hanauer, M., L\u00fcders, A., and Nennstiel, U. (2023). Is Our Newborn Screening Working Well? A Literature Review of Quality Requirements for Newborn Blood Spot Screening (NBS) Infrastructure and Procedures. Int. J. Neonatal Screen., 9.","DOI":"10.3390\/ijns9030035"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100311","DOI":"10.1016\/j.lanepe.2022.100311","article-title":"Newborn Screening as a Fully Integrated System to Stimulate Equity in Neonatal Screening in Europe","volume":"13","author":"Scarpa","year":"2022","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gaviglio, A., McKasson, S., Singh, S., and Ojodu, J. (2023). Infants with Congenital Diseases Identified Through Newborn Screening-United States, 2018\u20132020. Int. J. Neonatal Screen., 9.","DOI":"10.3390\/ijns9020023"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bedford, S., and Vachuska, K. (2024). Assessing Interstate Racial and Socioeconomic Disparities in Newborn Screening Policies in the United States. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1310516"},{"key":"ref_32","first-page":"100581","article-title":"Newborn Sequencing Is Only Part of the Solution for Better Child Health","volume":"25","author":"Brunelli","year":"2023","journal-title":"Lancet Reg. Health Am."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Clarke, L.A., Dickson, P., Ellinwood, N.M., and Klein, T.L. (2020). Newborn Screening for Mucopolysaccharidosis I: Moving Forward Learning from Experience. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6040091"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yu, S.H., Pollard, L., Wood, T., Flanagan-Steet, H., and Steet, R. (2020). A Biochemical Platform to Define the Relative Specific Activity of IDUA Variants Identified by Newborn Screening. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6040088"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Herbst, Z.M., Urdaneta, L., Klein, T., Burton, B.K., Basheeruddin, K., Liao, H.-C., Fuller, M., and Gelb, M.H. (2022). Evaluation of Two Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis Type II. Int. J. Neonatal Screen., 8.","DOI":"10.3390\/ijns8010009"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1373\/clinchem.2011.163139","article-title":"Digital Microfluidic Platform for Multiplexing Enzyme Assays: Implications for Lysosomal Storage Disease Screening in Newborns","volume":"57","author":"Sista","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Burton, B.K., Hickey, R., and Hitchins, L. (2020). Newborn Screening for Mucopolysaccharidosis Type II in Illinois: An Update. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6030073"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jpeds.2019.09.036","article-title":"Newborn Screening for Mucopolysaccharidoses: Results of a Pilot Study with 100 000 Dried Blood Spots","volume":"216","author":"Scott","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_39","unstructured":"American College of Medical Genetics and Genomics (2026, June 03). Newborn Screening ACT Sheet [Iduronate 2-Sulfatase Deficiency] Mucopolysaccharidosis Type II. Available online: https:\/\/www.acmg.net\/PDFLibrary\/MPS-II.pdf."},{"key":"ref_40","unstructured":"American College of Medical Genetics and Genomics (2026, June 03). Mucopolysacchardosis Type II (MPSII): Decreased Iduronate 2-Sulfatase (I2S) Activity (Algorithm). Available online: https:\/\/www.acmg.net\/PDFLibrary\/MPS-II-Algorithm.pdf."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Furnier, S.M., Durkin, M.S., and Baker, M.W. (2020). Translating Molecular Technologies into Routine Newborn Screening Practice. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6040080"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"D\u2019Avanzo, F., Rigon, L., Zanetti, A., and Tomanin, R. (2020). Mucopolysaccharidosis Type II: One Hundred Years of Research, Diagnosis, and Treatment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041258"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s40246-024-00701-w","article-title":"Molecular basis of mucopolysaccharidosis type II (Hunter syndrome): First review and classification of published IDS gene variants","volume":"18","author":"Zanetti","year":"2024","journal-title":"Hum. Genom."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ymgme.2022.07.016","article-title":"Long-Term Open-Label Extension Study of the Safety and Efficacy of Intrathecal Idursulfase-IT in Patients with Neuronopathic Mucopolysaccharidosis II","volume":"137","author":"Muenzer","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_45","unstructured":"Health Resources & Services Administration (2026, June 03). Newborn Screening Timeliness Goals, Available online: https:\/\/www.hrsa.gov\/advisory-committees\/heritable-disorders\/newborn-screening-timeliness."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109285","DOI":"10.1016\/j.ymgme.2025.109285","article-title":"Evaluation and follow-up of newborns screening positive for mucopolysaccharidosis II: Results from an international modified Delphi consensus","volume":"146","author":"Burton","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Washburn, J., and Millington, D.S. (2020). Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report. Int. J. Neonatal Screen., 6.","DOI":"10.3390\/ijns6040078"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ymgme.2016.12.010","article-title":"Glycosaminoglycan Levels in Dried Blood Spots of Patients with Mucopolysaccharidoses and Mucolipidoses","volume":"120","author":"Kubaski","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_49","unstructured":"Clinical and Laboratory Standards Institute (2023). Clinical and Laboratory Standards Institute Guideline NBS02\u2014Newborn Screening Follow-Up and Education, Clinical and Laboratory Standards Institute. [3rd ed.]. Available online: https:\/\/clsi.org\/standards\/products\/newborn-screening\/documents\/nbs02\/."},{"key":"ref_50","unstructured":"ACHDNC (2024, May 15). Communication Guide, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/resources\/achdnc-communication-guide-newborn.pdf."},{"key":"ref_51","unstructured":"(2024, October 19). Baby\u2019s First Test. Understanding and Communicating NBS Results Toolkit. Available online: https:\/\/www.babysfirsttest.org\/newborn-screening\/resources\/understanding-and-communicating-nbs-results-toolkit."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e33485","DOI":"10.2196\/33485","article-title":"Co-Designing Improved Communication of Newborn Bloodspot Screening Results to Parents: Mixed Methods Study","volume":"14","author":"Chudleigh","year":"2022","journal-title":"J. Particip. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Conway, M., Vuong, T.T., Hart, K., Rohrwasser, A., and Eilbeck, K. (2022). Pain Points in Parents\u2019 Interactions with Newborn Screening Systems: A Qualitative Study. BMC Pediatr., 22.","DOI":"10.1186\/s12887-022-03160-1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/cch.13105","article-title":"Parents\u2019 Experience of the Communication Process of Positivity at Newborn Screening for Metabolic Diseases: A Qualitative Study","volume":"49","author":"Bani","year":"2023","journal-title":"Child. Care Health Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1016\/j.pedn.2017.10.002","article-title":"Public Attitudes Toward Expanded Newborn Screening","volume":"38","author":"DeLuca","year":"2018","journal-title":"J. Pediatr. Nurs."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/JPN.0b013e3181a1bc1f","article-title":"Newborn Screening: An Appeal for Improved Parent Education","volume":"23","author":"Tluczek","year":"2009","journal-title":"J. Perinat. Neonatal Nurs."},{"key":"ref_57","unstructured":"BabyCenter LLC (2025, April 08). BabyCenter\u00ae. Available online: https:\/\/www.babycenter.com\/."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1097\/GIM.0b013e3182209f09","article-title":"What Questions Should Newborn Screening Long-Term Follow-Up Be Able to Answer? A Statement of the Us Secretary for Health and Human Services\u2019 Advisory Committee on Heritable Disorders in Newborns and Children","volume":"13","author":"Hinton","year":"2011","journal-title":"Genet. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Evans, A., LeBlanc, K., Bonhomme, N., Shone, S.M., Gaviglio, A., Freedenberg, D., Penn, J., Johnson, C., Vogel, B., and Dolan, S.M. (2019). A Newborn Screening Education Best Practices Framework: Development and Adoption. Int. J. Neonatal Screen., 5.","DOI":"10.3390\/ijns5020022"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Rocque, R., and Leanza, Y. (2015). A Systematic Review of Patients\u2019 Experiences in Communicating with Primary Care Physicians: Intercultural Encounters and a Balance Between Vulnerability and Integrity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139577"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Fusco, F., Chudleigh, J., Holder, P., Bonham, J.R., Southern, K.W., Simpson, A., Moody, L., Olander, E.K., Chinnery, H., and Morris, S. (2022). Delivering Positive Newborn Screening Results: Cost Analysis of Existing Practice Versus Innovative, Co-Designed Strategies from the ReSPoND Study. Int. J. Neonatal Screen., 8.","DOI":"10.3390\/ijns8010019"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s13023-023-02837-9","article-title":"Living with a Rare Disease\u2014Experiences and Needs in Pediatric Patients and Their Parents","volume":"18","author":"Witt","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7","DOI":"10.20517\/rdodj.2022.04","article-title":"The Importance of Psychological Support for Parents and Caregivers of Children with a Rare Disease at Diagnosis","volume":"1","author":"Kenny","year":"2022","journal-title":"Rare Dis. Orphan Drugs J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ymgme.2018.07.001","article-title":"Critical Review of Current MPS Guidelines and Management","volume":"126","author":"Stapleton","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_65","unstructured":"US Food and Drug Administration (2024, November 01). ELAPRASE\u00ae (Idursulfase) Injection, for Intravenous Use; Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/125151s197lbl.pdf."},{"key":"ref_66","unstructured":"European Medicines Agency (2024, November 01). Summary of Product Characteristics: Elaprase. Available online: https:\/\/ec.europa.eu\/health\/documents\/community-register\/2015\/20150914132981\/anx_132981_en.pdf."},{"key":"ref_67","unstructured":"Pharmaceuticals and Medical Devices Agency (2024, November 01). FY2007 List of Approved Products: New Drugs. Available online: https:\/\/www.pmda.go.jp\/files\/000267892.pdf."},{"key":"ref_68","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_69","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_70","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s13023-017-0712-3","article-title":"Clinical Outcomes in Idursulfase-Treated Patients with Mucopolysaccharidosis Type II: 3-Year Data from the Hunter Outcome Survey (HOS)","volume":"12","author":"Muenzer","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","unstructured":"Al-Hertani, W., Pathak, R.R., Evuarherhe, O., Carter, G., Schaeffer-Koziol, C.R., Whiteman, D.A.H., and Wright, E. (2024). Intravenous Idursulfase for the Treatment of Mucopolysaccharidosis Type II: A Systematic Literature Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168573"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/gim.2013.162","article-title":"A Multicenter, Open-Label Study Evaluating Safety and Clinical Outcomes in Children (1.4-7.5 Years) with Hunter Syndrome Receiving Idursulfase Enzyme Replacement Therapy","volume":"16","author":"Giugliani","year":"2014","journal-title":"Genet. Med."},{"key":"ref_74","first-page":"99","article-title":"Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age","volume":"14","author":"Lampe","year":"2014","journal-title":"JIMD Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e937527","DOI":"10.12659\/AJCR.937527","article-title":"An Infant Presenting with Interstitial Lung Disease Diagnosed Later as Hunter Syndrome: A Case Report","volume":"23","author":"AlTami","year":"2022","journal-title":"Am. J. Case Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymgme.2011.02.018","article-title":"Incidence and Timing of Infusion-Related Reactions in Patients with Mucopolysaccharidosis Type II (Hunter Syndrome) on Idursulfase Therapy in the Real-World Setting: A Perspective from the Hunter Outcome Survey (HOS)","volume":"103","author":"Burton","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ymthe.2020.09.039","article-title":"A Phase 2\/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II","volume":"29","author":"Okuyama","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_78","unstructured":"Pharmaceuticals and Medical Devices Agency (2025, March 18). Review Report\u2014Pabinafusp Alfa (Genetical Recombination). Available online: https:\/\/www.pmda.go.jp\/files\/000242410.pdf."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"102870","DOI":"10.1016\/j.gimo.2025.102870","article-title":"P026: Interim Analysis of the Efficacy and Safety of Weekly Intravenous Tividenofusp Alfa in Mucopolysaccharidosis Type II: A Phase 1\/2 Study","volume":"3","author":"Burton","year":"2025","journal-title":"Genet. Med. Open"},{"key":"ref_80","unstructured":"Denali Therapeutics (2025, September 17). Denali Therapeutics Announces FDA Acceptance and Priority Review of Biologics License Application (BLA) for Tividenofusp Alfa for Hunter Syndrome (MPS II). Available online: https:\/\/www.globenewswire.com\/news-release\/2025\/07\/07\/3110980\/0\/en\/Denali-Therapeutics-Announces-FDA-Acceptance-and-Priority-Review-of-Biologics-License-Application-BLA-for-Tividenofusp-Alfa-for-Hunter-Syndrome-MPS-II.html."},{"key":"ref_81","unstructured":"U.S. Food and Drug Administration (2026, April 08). FDA Approves Drug to Treat Neurologic Manifestations of Hunter Syndrome, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome."},{"key":"ref_82","unstructured":"National Library of Medicine (2025, September 17). A Multi-Cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients with Mucopolysaccharidosis Type II, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05208281."},{"key":"ref_83","unstructured":"Generium Pharmaceuticals (2026, July 14). Breakthrough in Hunter Syndrome Treatment: Original Drug for Mucopolysaccharidosis Type II Registered in Russia. Available online: https:\/\/www.generium.ru\/en\/news\/breakthrough-in-hunter-syndrome-treatment-original-drug-for-mucopolysaccharidosis-type-ii-registered\/."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"eaay8980","DOI":"10.1126\/scitranslmed.aay8980","article-title":"Tolerance Induction and Microglial Engraftment After Fetal Therapy Without Conditioning in Mice with Mucopolysaccharidosis Type VII","volume":"12","author":"Nguyen","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1056\/NEJMoa2200587","article-title":"In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe\u2019s Disease","volume":"387","author":"Cohen","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_86","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_87","doi-asserted-by":"crossref","unstructured":"Horgan, C., Jones, S.A., Bigger, B.W., and Wynn, R. (2022). Current and Future Treatment of Mucopolysaccharidosis (MPS) Type II: Is Brain-Targeted Stem Cell Gene Therapy the Solution for This Devastating Disorder?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094854"},{"key":"ref_88","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_89","doi-asserted-by":"crossref","first-page":"e8730","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_90","unstructured":"(2025, September 17). Regenxbio Announces FDA Review Extension of BLA for RGX-121 to Treat Patients with MPS II. Available online: https:\/\/ir.regenxbio.com\/news-releases\/news-release-details\/regenxbio-announces-fda-review-extension-bla-rgx-121-treat."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"101201","DOI":"10.1016\/j.omtm.2024.101201","article-title":"Comparative Dose Effectiveness of Intravenous and Intrathecal AAV9.CB7.hIDS, RGX-121, in Mucopolysaccharidosis Type II Mice","volume":"32","author":"Smith","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_92","first-page":"4164","article-title":"RGX-121 Gene Therapy for Severe Mucopolysaccharidosis Type II (MPS II): Interim Neurodevelopmental Outcomes and Biomarker Results (4164)","volume":"96","author":"Harmatz","year":"2021","journal-title":"Child. Neurol."},{"key":"ref_93","unstructured":"Giugliani, R. (2025, September 17). CAMPSIITE\u00ae Phase I\/II\/III: Interim Clinical Update of Clemidsogene Lanparvovec (RGX-121), an Investigational Gene Therapy for Treatment of Neuronopathic Mucopolysaccharidosis Type II (MPS II). Available online: https:\/\/www.regenxbio.com\/getmedia\/5b470e1c-62f3-429e-94ea-1a4db12e3639\/CAMPSIITE-RGX-121-ICIEM-Final-September-2025.pdf?ext=.pdf."},{"key":"ref_94","unstructured":"Regenxbio (2026, April 08). REGENXBIO Announces Regulatory Update on RGX-121 BLA for MPS II. Available online: https:\/\/ir.regenxbio.com\/news-releases\/news-release-details\/regenxbio-announces-regulatory-update-rgx-121-bla-mps-ii\/."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s10545-017-0075-x","article-title":"Survival in Idursulfase-Treated and Untreated Patients with Mucopolysaccharidosis Type II: Data from the Hunter Outcome Survey (HOS)","volume":"40","author":"Burton","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1186\/s13023-021-02052-4","article-title":"Evaluation of the Long-Term Treatment Effects of Intravenous Idursulfase in Patients with Mucopolysaccharidosis II (MPS II) Using Statistical Modeling: Data from the Hunter Outcome Survey (HOS)","volume":"16","author":"Muenzer","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/GIM.0b013e318206786f","article-title":"Idursulfase Treatment of Hunter Syndrome in Children Younger Than 6 Years: Results from the Hunter Outcome Survey","volume":"13","author":"Muenzer","year":"2011","journal-title":"Genet. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.pepo.2017.03.022","article-title":"Long-Term Clinical Effects of Enzyme Replacement Therapy in MPS II","volume":"92","author":"Jamroz","year":"2017","journal-title":"Pediatr. Pol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ymgme.2022.07.017","article-title":"Intrathecal Idursulfase-IT in Patients With Neuronopathic Mucopolysaccharidosis II: Results From a Phase 2\/3 Randomized Study","volume":"137","author":"Muenzer","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"107709","DOI":"10.1016\/j.ymgme.2023.107709","article-title":"Intracerebroventricular Enzyme Replacement Therapy in Patients with Neuronopathic Mucopolysaccharidosis Type II: Final Report of 5-Year Results from a Japanese Open-Label Phase 1\/2 Study","volume":"140","author":"Seo","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s41687-019-0140-3","article-title":"Assessing the Impact on Caregivers Caring for Patients with Rare Pediatric Lysosomal Storage Diseases: Development of the Caregiver Impact Questionnaire","volume":"3","author":"Harrington","year":"2019","journal-title":"J. Patient Rep. Outcomes"},{"key":"ref_102","unstructured":"Kemper, A.R., Lam, K.K., Letostak, T., Grosse, S.D., Ojodu, J., Prosser, L.A., Ream, M., Bocchini, J.A., Botkin, J.R., and Comeau, A.M. (2024, August 09). Evidence-Based Review of Newborn Screening for Mucopolysaccharidosis Type II: Final Report, Available online: https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/meetings\/mps-ii-final-report-3-28-2022.pdf."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.2196\/jmir.5834","article-title":"Internet Use by Parents of Children with Rare Conditions: Findings from a Study on Parents\u2019 Web Information Needs","volume":"19","author":"Nicholl","year":"2017","journal-title":"J. Med. Internet Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Nori, M., Fisher-Vance, D., Wuerth, L., Colenso, R., and Donovan, D.J. (2022). The Global Role of Patients, Advocates and Caregivers in Rare Diseases. Future Rare Dis., 2.","DOI":"10.2217\/frd-2022-0003"}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/3\/66\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:12:08Z","timestamp":1786680728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/12\/3\/66"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":104,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijns12030066"],"URL":"https:\/\/doi.org\/10.3390\/ijns12030066","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}