Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Hurler Syndrome

Pre-transplant risk factors affecting outcome in Hurler syndrome

Abstract

Allogeneic transplantation remains the standard of care for patients with Hurler syndrome. As enzyme replacement therapy (ERT) has become available, controversy has emerged in regards to whether the use of enzyme in the peri-transplant period is appropriate. An analysis was performed on 74 patients with Hurler syndrome transplanted at the University of Minnesota between 1990 and 2003, before our use of ERT associated with transplant, with the intention of determining if patients at higher risk during the transplant can be identified based on evaluations and events before transplantation. Age, the presence of hydrocephalus, a history of cardiovascular issues or upper airway obstruction before transplant was not associated with significant differences in survival. In contrast, patients who had a history of lower airway disease, including reactive airway disease or bronchiolitis, or a history of pneumonia, had a significantly inferior outcome based on OS. The risk for serious respiratory complications was also assessed by evaluating the incidence of intubation. Overall, 31% of these patients were intubated. The risk of intubation was higher in older patients and in those with a history of lower airway disease. These findings have implications for the care of patients with high-risk features.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Bach G, Friedman R, Weissmann B, Neufeld EF . The defect in the Hurler and Scheie syndromes: deficiency of α-L-iduronidase. Proc Natl Acad Sci USA 1972; 69: 2048–2051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ . Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat 1995; 6: 288–302.

    Article  CAS  PubMed  Google Scholar 

  3. Pastores GM, Arn P, Beck M, Clarke JT, Guffon N, Kaplan P 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 2007; 91: 37–47.

    Article  CAS  PubMed  Google Scholar 

  4. Muenzer J, Wraith JE, Clarke LA . Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 2009; 123: 19–29.

    Article  PubMed  Google Scholar 

  5. Peters C, Balthazor M, Shapiro EG, King RJ, Kollman C, Hegland JD et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996; 87: 4894–4902.

    CAS  PubMed  Google Scholar 

  6. Peters C, Shapiro EG, Anderson J, Henslee-Downey PJ, Klemperer MR, Cowan MJ et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood 1998; 91: 2601–2608.

    CAS  PubMed  Google Scholar 

  7. Shapiro EG, Lockman LA, Balthazor M, Krivit W . Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis 1995; 18: 413–429.

    Article  CAS  PubMed  Google Scholar 

  8. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J 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 2004; 144: 581–588.

    Article  CAS  PubMed  Google Scholar 

  9. Wraith EJ, Hopwood JJ, Fuller M, Meikle PJ, Brooks DA . Laronidase treatment of mucopolysaccharidosis I. BioDrugs 2005; 19: 1–7.

    Article  CAS  PubMed  Google Scholar 

  10. Miebach E . Enzyme replacement therapy in mucopolysaccharidosis type I. Acta Paediatr Suppl 2005; 94: 58–60; discussion 57.

    Article  CAS  PubMed  Google Scholar 

  11. Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L et al. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant 2008; 41: 531–535.

    Article  CAS  PubMed  Google Scholar 

  12. Cox-Brinkman J, Boelens JJ, Wraith JE, O’Meara A, Veys P, Wijburg FA et al. Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome. Bone Marrow Transplant 2006; 38: 17–21.

    Article  CAS  PubMed  Google Scholar 

  13. Boelens JJ, Wynn RF, O’Meara A, Veys P, Bertrand Y, Souillet G et al. Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant 2007; 40: 225–233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P et al. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 2004; 350: 1960–1969.

    Article  CAS  PubMed  Google Scholar 

  15. Boelens JJ . Trends in haematopoietic cell transplantation for inborn errors of metabolism. J Inherit Metab Dis 2006; 29: 413–420.

    Article  PubMed  Google Scholar 

  16. Kharbanda S, Panoskaltsis-Mortari A, Haddad IY, Blazar BR, Orchard PJ, Cornfield DN et al. Inflammatory cytokines and the development of pulmonary complications after allogeneic hematopoietic cell transplantation in patients with inherited metabolic storage disorders. Biol Blood Marrow Transplant 2006; 12: 430–437.

    Article  CAS  PubMed  Google Scholar 

  17. Gassas A, Sung L, Doyle JJ, Clarke JT, Saunders EF . Life-threatening pulmonary hemorrhages post bone marrow transplantation in Hurler syndrome. Report of three cases and review of the literature. Bone Marrow Transplant 2003; 32: 213–215.

    Article  CAS  PubMed  Google Scholar 

  18. Grewal SS, Wynn R, Abdenur JE, Burton BK, Gharib M, Haase C et al. Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome. Genet Med 2005; 7: 143–146.

    Article  CAS  PubMed  Google Scholar 

  19. Soni S, Hente M, Breslin N, Hersh J, Whitley C, Cheerva A et al. Pre-stem cell transplantation enzyme replacement therapy in Hurler syndrome does not lead to significant antibody formation or delayed recovery of the endogenous enzyme post-transplant: a case report. Pediatr Transplant 2007; 11: 563–567.

    Article  PubMed  Google Scholar 

  20. Tokic V, Barisic I, Huzjak N, Petkovic G, Fumic K, Paschke E . Enzyme replacement therapy in two patients with an advanced severe (Hurler) phenotype of mucopolysaccharidosis I. Eur J Pediatr 2007; 166: 727–732.

    Article  PubMed  Google Scholar 

  21. Aldenhoven M, Boelens JJ, de Koning TJ . The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 2008; 14: 485–498.

    Article  CAS  PubMed  Google Scholar 

  22. Belani KG, Krivit W, Carpenter BL, Braunlin E, Buckley JJ, Liao JC et al. Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings. J Pediatr Surg 1993; 28: 403–408; discussion 408–410.

    Article  CAS  PubMed  Google Scholar 

  23. Herrick IA, Rhine EJ . The mucopolysaccharidoses and anaesthesia: a report of clinical experience. Can J Anaesth 1988; 35: 67–73.

    Article  CAS  PubMed  Google Scholar 

  24. Baines D, Keneally J . Anaesthetic implications of the mucopolysaccharidoses: a fifteen-year experience in a children's hospital. Anaesth Intensive Care 1983; 11: 198–202.

    Article  CAS  PubMed  Google Scholar 

  25. Nuckols JD . Autopsy findings in umbilical cord blood transplant recipients. Am J Clin Pathol 1999; 112: 335–342.

    Article  CAS  PubMed  Google Scholar 

  26. Tolar J, Orchard PJ, Key NS, Blazar BR . Circulating anticoagulant glycosaminoglycans in mucopolysaccharidosis type I. J Thromb Haemost 2008; 6: 893–895.

    Article  CAS  PubMed  Google Scholar 

  27. Boelens JJ, Rocha V, Aldenhoven M, Wynn R, O’Meara A, Michel G et al. Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with Hurler syndrome. Biol Blood Marrow Transplant 2009; 15: 618–625.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the Children's Cancer Research Fund (CCRF), as well as by an anonymous private foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P J Orchard.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orchard, P., Milla, C., Braunlin, E. et al. Pre-transplant risk factors affecting outcome in Hurler syndrome. Bone Marrow Transplant 45, 1239–1246 (2010). https://doi.org/10.1038/bmt.2009.319

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.319

Keywords

This article is cited by

Search

Quick links