{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:18:01Z","timestamp":1790007481120,"version":"4.0.1"},"reference-count":21,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"OBJECTIVE. Our objective was to evaluate the safety, pharmacokinetics, and efficacy of laronidase in young, severely affected children with mucopolysaccharidosis I.<\/jats:p>\n METHODS. This was a prospective, open-label, multinational study of 20 patients who had mucopolysaccharidosis I and were &lt;5 years old (16 with Hurler syndrome, 4 with Hurler-Scheie syndrome) and were scheduled to receive intravenous laronidase at 100 U\/kg (0.58 mg\/kg) weekly for 52 weeks. Four patients underwent dosage increases to 200 U\/kg for the last 26 weeks because of elevated urinary glycosaminoglycan levels at week 22.<\/jats:p>\n RESULTS. Laronidase was well tolerated at both dosages. Investigators reported improved clinical status in 94% of patients at week 52. The mean urinary glycosaminoglycan level declined by \u223c50% at week 13 and was sustained thereafter. A more robust decrease in urinary glycosaminoglycan was observed in patients with low antibody levels and those who were receiving the 200 U\/kg dosage. On examination, the liver edge was reduced by 69.5% in patients with a palpable liver at baseline and week 52 (n = 10). The proportion of patients with left ventricular hypertrophy decreased from 53% to 17%. Global assessment of sleep studies showed improvement or stabilization in 67% of patients, and the apnea\/hypopnea index decreased by 5.8 events per hour (\u22128.5%) in those with abnormal baseline values. The younger patients with Hurler syndrome (&lt;2.5 years) and all 4 patients with Hurler-Scheie syndrome showed normal mental development trajectories during the 1-year treatment period.<\/jats:p>\n CONCLUSIONS. Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are &lt;5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation.<\/jats:p>","DOI":"10.1542\/peds.2006-2156","type":"journal-article","created":{"date-parts":[[2007,7,2]],"date-time":"2007-07-02T12:35:25Z","timestamp":1183379725000},"page":"e37-e46","source":"Crossref","is-referenced-by-count":215,"title":["Enzyme Replacement Therapy in Patients Who Have Mucopolysaccharidosis I and Are Younger Than 5 Years: Results of a Multinational Study of Recombinant Human \u03b1-\n l<\/scp>\n -Iduronidase (Laronidase)"],"prefix":"10.1542","volume":"120","author":[{"given":"J. Edmond","family":"Wraith","sequence":"first","affiliation":[{"name":"Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital, University of Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Lane","sequence":"additional","affiliation":[{"name":"Sleep and Respiratory Services, Great Ormond Street Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sophia Children's Hospital, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Division of Pediatric Clinical Neuroscience, University of Minnesota, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xue","sequence":"additional","affiliation":[{"name":"Genzyme Europe BV, Naarden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil D.","family":"Kakkis","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc, Novato, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Guffon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centre de Re\u0301fe\u0301rence des Maladies He\u0301re\u0301ditaires du Me\u0301tabolisme, Ho\u0302pital Edouard Herriot, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"2021120901555939300_R1","unstructured":"Neufeld E, Muenzer J. 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