Abstract
Mucopolysaccharidosis (MPS) II, or Hunter syndrome, is a lysosomal storage disease characterized by multi-systemic involvement and a progressive clinical course. Enzyme replacement therapy with idursulfase has been approved in more than 50 countries worldwide; however, safety and efficacy data from clinical studies are currently only available for patients 1.4 years of age and older. Sibling case studies of infants with MPS I, II, and VI who initiated ERT in the first weeks or months of life have reported no new safety concerns and a more favorable clinical course for the sibling treated in infancy than for the later-treated sibling. Here we describe our experiences with a case series of eight MPS II patients for whom idursulfase treatment was initiated at under 1 year of age. The majority of the patients were diagnosed because of a family history of disease. All of the infants displayed abnormalities consistent with MPS II at diagnosis. The youngest age at treatment start was 10 days and the oldest was 6.5 months, with duration of treatment varying between 6 weeks and 5.5 years. No new safety concerns were observed, and none of the patients experienced an infusion-related reaction. All of the patients treated for more than 6 weeks showed improvements and/or stabilization of some somatic manifestations while on treatment. In some cases, caregivers made comparisons with other affected family members and reported that the early-treated patients experienced a less severe clinical course, although a lack of medical records for many family members precluded a rigorous comparison.
Competing interests: None declared
Authorship Statement: All authors other than the first author contributed equally to this work. Authors are listed in alphabetical order after the first author.
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Abbreviations
- CT:
-
Computed tomography
- ERT:
-
Enzyme replacement therapy
- GAG:
-
Glycosaminoglycan
- HSCT:
-
Hematopoietic stem cell transplantation
- I2S:
-
Iduronate-2-sulfatase
- IRR:
-
Infusion-related reaction
- IV:
-
Intravenous
- LSD:
-
Lysosomal storage disorder
- MPS:
-
Mucopolysaccharidosis
- MRI:
-
Magnetic resonance imaging
- uGAG:
-
Urinary glycosaminoglycan
References
Baldo G, Matte U, Artigalas O et al (2011) Placenta analysis of prenatally diagnosed patients reveals early GAG storage in mucopolysaccharidoses II and VI. Mol Genet Metab 103:197–198
Burton BK, Whiteman DA (2011) 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). Mol Genet Metab 103:113–120
de Ru MH, Boelens JJ, Das AM et al (2011) Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis 6:55
Froissart R, Maire I, Millat G et al (1998) Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients. Clin Genet 53:362–368
Gabrielli O, Clarke LA, Bruni S, Coppa GV (2010) Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up. Pediatrics 125:e183–e187
Giugliani R, Hwu P, Tylki-Szymanska A, Whiteman DAH, Pano A (2013) 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. Genet Med. doi:10.1038/gim.2013.162
Jones SA, Almassy Z, Beck M et al (2009) Mortality and cause of death in mucopolysaccharidosis type II-a historical review based on data from the Hunter Outcome Survey (HOS). J Inherit Metab Dis 32:534–543
Kampmann C, Beck M, Morin I, Loehr JP (2011) Prevalence and characterization of cardiac involvement in Hunter syndrome. J Pediatr 159(327–331):e322
Martin R, Beck M, Eng C et al (2008) Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 121:e377–e386
McGill JJ, Inwood AC, Coman DJ et al (2010) Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age–a sibling control study. Clin Genet 77:492–498
Muenzer J, Wraith JE, Beck M et al (2006) A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 8:465–473
Muenzer J, Beck M, Eng CM et al (2009) Multidisciplinary management of Hunter syndrome. Pediatrics 124:e1228–e1239
Muenzer J, Beck M, Giugliani R et al (2011a) Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. Genet Med 13:102–109
Muenzer J, Bodamer O, Burton B et al (2012) The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr 171:181–188
Nakamura K, Hattori K, Endo F (2011) Newborn screening for lysosomal storage disorders. Am J Med Genet C Semin Med Genet 157:63–71
Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, vol III. McGraw-Hill, New York, pp 3421–3452
Rathmann M, Bunge S, Beck M, Kresse H, Tylki-Szymanska A, Gal A (1996) Mucopolysaccharidosis type II (Hunter syndrome): mutation “hot spots” in the iduronate-2-sulfatase gene. Am J Hum Genet 59:1202–1209
Scarpa M, Almassy Z, Beck M et al (2011) Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. Orphanet J Rare Dis 6:72
Schulze-Frenking G, Jones SA, Roberts J, Beck M, Wraith JE (2011) Effects of enzyme replacement therapy on growth in patients with mucopolysaccharidosis type II. J Inherit Metab Dis 34:203–208
Shire Human Genetic Therapies (2013) Elaprase® (idursulfase) solution for intravenous infusion [prescribing information]. Shire Human Genetic Therapies, Inc., Lexington, MA
Tajima G, Sakura N, Kosuga M, Okuyama T, Kobayashi M (2013) Effects of idursulfase enzyme replacement therapy for mucopolysaccharidosis type II when started in early infancy: comparison in two siblings. Mol Genet Metab 108:172–177
Tomatsu S, Gutierrez MA, Ishimaru T et al (2005) Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses. J Inherit Metab Dis 28:743–757
Tylki-Szymanska A, Jurecka A, Zuber Z, Rozdzynska A, Marucha J, Czartoryska B (2012) Enzyme replacement therapy for mucopolysaccharidosis II from 3 months of age: a 3-year follow-up. Acta Paediatr 101:e42–e47
Vafiadaki E, Cooper A, Heptinstall LE, Hatton CE, Thornley M, Wraith JE (1998) Mutation analysis in 57 unrelated patients with MPS II (Hunter’s disease). Arch Dis Child 79:237–241
Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J (2008) Initial report from the Hunter Outcome Survey. Genet Med 10:508–516
Young ID, Harper PS (1983) The natural history of the severe form of Hunter’s syndrome: a study based on 52 cases. Dev Med Child Neurol 25:481–489
Young ID, Harper PS, Archer IM, Newcombe RG (1982a) A clinical and genetic study of Hunter’s syndrome. 1. Heterogeneity. J Med Genet 19:401–407
Young ID, Harper PS, Newcombe RG, Archer IM (1982b) A clinical and genetic study of Hunter’s syndrome. 2. Differences between the mild and severe forms. J Med Genet 19:408–411
Acknowledgments
We would like to thank all the patients and families for their participation. Editorial assistance to the authors was provided by Jillian Lokere, MS, of The Curry Rockefeller Group, LLC, Tarrytown, New York, and was funded by Shire. The authors received no payment for their work, and they confirm independence from the funding source.
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Communicated by: Douglas A Brooks, PhD
Appendices
Synopsis
In a case series of eight MPS II patients treated with idursulfase enzyme replacement therapy started under 1 year of age, treatment was well tolerated and produced some somatic improvements, with no new safety concerns seen.
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Individual Contributions
The planning, writing, and content decisions for the manuscript were performed by all the authors equally.
Financial Disclosure
Editorial assistance to the authors was provided by Jillian Lokere, MS, of The Curry Rockefeller Group, LLC, Tarrytown, New York and was funded by Shire. The sponsor played no role in the writing of this report. The authors received no payment for their work. The authors confirm independence from the funding source.
Conflict of Interest Statements
Christina Lampe, M.D., has received grants and/or speaker honoraria and/or research grants from BioMarin Pharmaceutical, and Shire. Andrea Atherton, MS, GCG, has received travel and educational grants and/or speaker honoraria and/or has participated on advisory boards from BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Barbara Burton, M.D., has received funding for the conduct of clinical trials from BioMarin Pharmaceutical, Genzyme Corporation, Shire, and Synageva BioPharma, and consulting fees and/or honoraria from BioMarin Pharmaceutical, Genzyme Corporation, Hyperion Therapeutics, and Shire. Maria Descartes, M.D., has nothing to declare. Roberto Giugliani, M.D., Ph.D., has received travel grants and/or speaker honoraria and/or investigator fees from Actelion Pharmaceuticals, Amicus Therapeutics, BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Dafne D.G. Horovitz, M.D., has received educational travel grants and/or speaker honoraria from BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Sandra Obikawa Kyosen, M.D., has received travel grants from BioMarin Pharmaceutical and Genzyme Corporation. Tatiana S.P.C. Magalhães, M.D., has received travel grants from BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Ana Maria Martins, M.D., has received travel grants and/or speaker honoraria and/or investigator fees from Actelion Pharmaceuticals, BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Nancy J. Mendelsohn, M.D. has received financial reimbursement for travel expenses and honoraria from BioMarin Pharmaceutical and Shire; she has provided consulting support to Genzyme Corporation, and is also engaged in ongoing research projects with BioMarin Pharmaceutical, Genzyme Corporation, and Shire. Joseph Muenzer, M.D., Ph.D., has received travel expense reimbursement and honoraria for speaking from BioMarin Pharmaceutical, Genzyme Corporation, and Shire. He has served on advisory boards and has been a principal investigator for MPS I and MPS II enzyme replacement clinical trials for BioMarin Pharmaceutical, Genzyme Corporation, and Shire. He is currently the principal investigator for a phase I/II intrathecal enzyme replacement clinical trial for the severe form of MPS II sponsored by Shire. Laurie D. Smith, M.D., Ph.D., has served on advisory boards for Shire.
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Consent to publish identifying information and facial images was obtained from all parents/guardians of patients for whom identifying information is included in this report.
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Lampe, C. et al. (2014). Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 14. JIMD Reports, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_289
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DOI: https://doi.org/10.1007/8904_2013_289
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