Summary
Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a progressive, multisystemic disease caused by a deficiency of iduronate-2-sulfatase. Patients with the severe form of the disease have cognitive impairment and typically die in the second decade of life. Patients with the less severe form do not experience significant cognitive involvement and may survive until the fifth or sixth decade of life. We studied the relationship of both severity of MPS II and the time period in which patients died with age at death in 129 patients for whom data were entered retrospectively into HOS (Hunter Outcome Survey), the only large-scale, multinational observational study of patients with MPS II. Median age at death was significantly lower in patients with cognitive involvement compared with those without cognitive involvement (11.7 versus 14.1 years; p = 0.024). These data indicate that cognitive involvement is indicative of more severe disease and lower life expectancy in patients with MPS II. Median age at death was significantly lower in patients who died in or before 1985 compared with those who died after 1985 (11.3 versus 14.1 years; p α 0.001). The difference in age at death between patients dying in or before, relative to after, the selected cut-off date of 1985 may reflect improvements in patient identification, care and management over the past two decades. Data from patients who died after 1985 could serve as a control in analyses of the effects of enzyme replacement therapy with idursulfase on mortality in patients with MPS II.
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Abbreviations
- BMT:
-
bone marrow transplantation
- ERT:
-
enzyme replacement therapy
- HOS:
-
Hunter Outcome Survey
- I2S:
-
iduronate-2-sulfatase
- MPS II:
-
mucopolysaccharidosis type II
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Acknowledgements
HOS is supported by Shire HGT, Inc., which is responsible for maintaining the central database and for performing statistical analyses at the request of the HOS advisory board. Shire HGT had no role in the interpretation of data. Editorial assistance to the authors was provided by Oxford PharmaGenesis™ Ltd and was paid for by Shire HGT, Inc.
The following physicians have contributed patient data to HOS as of May 15, 2008: Thomas Kroepfl, Graz, Austria; Olaf Bodamer, Vienna, Austria; Linda De Meirleir, Brussels, Belgium; Dantón Melgar, Santa Cruz de la Sierra, Bolivia; Roberto Giugliani, Porto Alegre, Brazil; Raquel Boy, Dafne Horovitz, Rio de Janeiro, Brazil; Radka Tincheva, Sofia, Bulgaria; Joe Clarke, Toronto, Canada; Lorne Clarke, Vancouver, Canada; Paulina Mabe, Santiago, Chile; Ingeborg Barišić, Ivo Barić, Zagreb, Croatia; Jiri Zeman, Prague, Czech Republic; Allan Meldgaard Lund, Copenhagen, Denmark; Nathalie Guffon, Lyon, France; Vassili Valayannopoulos, Bénédicte Héron, Paris, France; Michael Beck, Gudrun Schulze Frenking, Mainz, Germany; Nicole Muschol, Hamburg, Germany; Dimitrios Zafeiriou, Thessaloniki, Greece; Zsuzsanna Almássy, Budapest, Hungary; Orazio Gabrielli, Ancona, Italy; Alessandro Cicognani, Bologna, Italy; Maja DiRocco, Genova, Italy; Rossella Parini, Monza, Italy; Maurizio Scarpa, Padova, Italy; Claudio Feliciani, Roberta Ricci, Rome, Italy; Ana Gaspar, Lisbon; Portugal; Elisa Leao Teles, Esmeralda Martina, Porto, Portugal; Peter Novikov, Moscow, Russia; Guillem Pintos, Badalona, Spain; Enrique Galán, Badajoz, Spain; Mireia del Toro, Merce Pineda, Barcelona, Spain; Luis Aldámiz, Bilbao, Spain, Milagros Marti Herrero, Las Palmas, Spain; Pilar Munguira, Linares, Spain; Luis González Gutiérrez-Solana, Madrid, Spain; Rosario Domingo, Murcia, Spain; Gemma Novoa, Ourense, Spain; Begoña de Azua, Palma de Mallorca, Spain; Dolores Lluch, Seville, Spain; Jaime Dalmau, Valencia, Spain; José Manuel Muro, Valladolid, Spain; Antonio Baldellou, Juan Pérez Calvo, Zaragoza, Spain; Nils Nilsson, Halmstad, Sweden; Dominiki Papadopoulou, Lund, Sweden; Gunilla Malm, Stockholm, Sweden; Shuan-Pei Lin, Taipei, Taiwan; Ans van der PLoeg, Rotterdam, The Netherlands; Chris Hendriksz, Birmingham, UK; Patrick Deegan, Uma Ramaswami, Cambridge, UK; Ashok Vellodi, London, UK; Simon Jones, Edmond Wraith, Manchester, UK; Paul Fernhoff, Atlanta, GA, USA; Ada Hamosh, Baltimore, MD, USA; Nancy Leslie, Cincinnati, OH, USA; Joseph Muenzer, Chapel Hill, NC, USA; William Wilson, Charlottesville, VA, USA; Barbara Burton, Chicago, IL, USA; Janet Thomas, Denver, CO, USA; Robert Greenstein, Hartford, CT, USA; Christine Eng, Houston, TX, USA; Sara Copeland, Iowa City, IA, USA; Charles Peters, Laurie Smith, Kansas City, MO, USA; John Moeschler, Lebanon, NH, USA, Parul Jayakar, Miami, FL, USA; Nancy Mendelsohn, Chester Whitley, Minneapolis, MN, USA; Greg Pastories, New York, NY, USA; Virginia Proud, Norfolk, VA, USA; Paul Harmatz, Oakland, CA, USA; Brad Schaefer, Omaha, NE, USA; Kirk Aleck, Phoenix, AZ, USA; Robert Steiner, Portland, OR, USA; David Viskochil, Salt Lake City, UT, USA, Laura Keppen, Sioux Falls, SD, USA; Cynthia Tifft, Washington, DC, USA.
The investigators would like to thank the patients and their families for their participation in HOS. We also wish to thank the UK MPS society, especially Mrs Christine Lavery, for careful and sensitive collection of cases over many years.
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Communicating editor: Gregory Pastores
Competing Interests: HOS is supported by Shire HGT, Inc., which is responsible for maintaining the central database and for performing statistical analyses at the request of the HOS advisory board. Shire HGT had no role in the interpretation of data. Editorial assistance to the authors was provided by Oxford PharmaGenesis™ Ltd and was paid for by Shire HGT, Inc.
References to electronic databases. Mucopolysaccharidosis type II (MPS II, Hunter syndrome: OMIM +309900. Iduronate-2-sulfatase: EC 3.1.6.13.
References to electronic databases: Mucopolysaccharidosis type II (MPS II, Hunter syndrome: OMIM +309900. Iduronate-2-sulfatase: EC 3.1.6.13.
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Jones, S.A., Almássy, Z., Beck, M. et al. 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 (2009). https://doi.org/10.1007/s10545-009-1119-7
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DOI: https://doi.org/10.1007/s10545-009-1119-7