{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:43:54Z","timestamp":1772268234188,"version":"3.50.1"},"reference-count":15,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:p>Mucopolysaccharidosis type I (MPS I) is a progressive and multisystemic disease, even in its attenuated Hurler-Scheie and Scheie forms. Clinical trials of enzyme-replacement therapy in MPS I have shown clinical benefit in patients with considerable preexisting disease, but no data exist on the effect of beginning enzyme replacement before the onset of significant clinical signs of disease. Here we present the 5-year follow-up of a boy with attenuated MPS I who had laronidase therapy initiated at the age of 5 months and compare his clinical course to that of his older sister, who began treatment at 5 years of age after she had developed typical signs of MPS I. After 5 years of treatment, the younger sibling has not developed any clinical manifestations of MPS I except for mild corneal clouding. In contrast, although many of the older sibling's clinical features have improved after 5 years of treatment, her dysostosis multiplex, cardiac valve involvement, and corneal clouding, although stabilized, have persisted. We suggest that early treatment of attenuated MPS I may significantly delay or prevent the onset of the major clinical signs, substantially modifying the natural history of the disease.<\/jats:p>","DOI":"10.1542\/peds.2009-1728","type":"journal-article","created":{"date-parts":[[2009,12,22]],"date-time":"2009-12-22T01:34:22Z","timestamp":1261445662000},"page":"e183-e187","source":"Crossref","is-referenced-by-count":99,"title":["Enzyme-Replacement Therapy in a 5-Month-Old Boy With Attenuated Presymptomatic MPS I: 5-Year Follow-up"],"prefix":"10.1542","volume":"125","author":[{"given":"Orazio","family":"Gabrielli","sequence":"first","affiliation":[{"name":"Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorne A.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Bruni","sequence":"additional","affiliation":[{"name":"Genzyme Italia, Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni V.","family":"Coppa","sequence":"additional","affiliation":[{"name":"Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2010,1,1]]},"reference":[{"key":"2021120821202046100_R1","unstructured":"Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver C, Beaudet A, Sly W, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2001:3421\u20133452"},{"key":"2021120821202046100_R2","doi-asserted-by":"crossref","unstructured":"Muenzer J, Wraith JE, Clarke LA; International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics.\u20082009;123(1):19\u201329","DOI":"10.1542\/peds.2008-0416"},{"key":"2021120821202046100_R3","doi-asserted-by":"crossref","unstructured":"Moore D, Connock MJ, Wraith E, Lavery C. The prevalence of and survival in mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK. Orphanet J Rare Dis.\u20082008;3:24","DOI":"10.1186\/1750-1172-3-24"},{"key":"2021120821202046100_R4","doi-asserted-by":"crossref","unstructured":"Terlato NJ, Cox GF. Can mucopolysaccharidosis type I disease severity be predicted based on a patient's genotype? A comprehensive review of the literature. Genet Med.\u20082003;5(4):286\u2013294","DOI":"10.1097\/01.GIM.0000078027.83236.49"},{"key":"2021120821202046100_R5","doi-asserted-by":"crossref","unstructured":"Vijay S, Wraith JE. Clinical presentation and follow-up of patients with the attenuated phenotype of mucopolysaccharidosis type I. Acta Paediatr. 2005;94(7):872\u2013877","DOI":"10.1111\/j.1651-2227.2005.tb02004.x"},{"key":"2021120821202046100_R6","doi-asserted-by":"crossref","unstructured":"Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001;344(3):182\u2013188","DOI":"10.1056\/NEJM200101183440304"},{"key":"2021120821202046100_R7","doi-asserted-by":"crossref","unstructured":"Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-l-iduronidase (laronidase). J Pediatr.\u20082004;144(5):581\u2013588","DOI":"10.1016\/j.jpeds.2004.01.046"},{"key":"2021120821202046100_R8","doi-asserted-by":"crossref","unstructured":"Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human \u03b1-l-iduronidase (laronidase). Pediatrics.\u20082007;120(1). Available at: www.pediatrics.org\/cgi\/content\/full\/120\/1\/e37","DOI":"10.1542\/peds.2006-2156"},{"key":"2021120821202046100_R9","doi-asserted-by":"crossref","unstructured":"Clarke L, Wraith JE, Beck M, et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics.\u20082009;123(1):229\u2013240","DOI":"10.1542\/peds.2007-3847"},{"key":"2021120821202046100_R10","doi-asserted-by":"crossref","unstructured":"Giugliani R, Mun\u0303oz Rojas V, Martins A, et al. A dose-optimization trial of laronidase (Aldurazyme) in patients with mucopolysaccharidosis I. Mol Genet Metab.\u20082009;96(1):13\u201319","DOI":"10.1016\/j.ymgme.2008.10.009"},{"key":"2021120821202046100_R11","doi-asserted-by":"crossref","unstructured":"Braunlin EA, Berry JM, Whitley CB. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am J Cardiol.\u20082006;98(3):416\u2013418","DOI":"10.1016\/j.amjcard.2006.02.047"},{"key":"2021120821202046100_R12","doi-asserted-by":"crossref","unstructured":"Sifuentes M, Doroshow R, Hoft R, et al. A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab.\u20082007;90(2):171\u2013180","DOI":"10.1016\/j.ymgme.2006.08.007"},{"key":"2021120821202046100_R13","doi-asserted-by":"crossref","unstructured":"Rempel BP, Clarke LA, Withers SG. A homology model for human alpha-l-iduronidase: insights into human disease. Mol Genet Metab.\u20082005;85(1):28\u201337","DOI":"10.1016\/j.ymgme.2004.12.006"},{"key":"2021120821202046100_R14","doi-asserted-by":"crossref","unstructured":"Pastores G, Arn P, Beck M, et al. The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with mucopolysaccharidosis type I. Mol Genet Metab.\u20082007;91(1):37\u201347","DOI":"10.1016\/j.ymgme.2007.01.011"},{"key":"2021120821202046100_R15","doi-asserted-by":"crossref","unstructured":"Simonaro C, D'Angelo M, Haskins M, Schuchman E. Joint and bone disease in the mucopolysaccharidoses: identification of new therapeutic targets and biomarkers using animal models. 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