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JIMD Reports - Volume 10 pp 119–123Cite as

Fatal and Unanticipated Cardiorespiratory Disease in a Two-Year-Old Child with Hurler Syndrome Following Successful Stem Cell Transplant

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Part of the book series: JIMD Reports ((JIMD,volume 10))

Abstract

A 2-year-old female with Hurler syndrome (mucopolysaccharidosis type 1) died suddenly within 3 months of successful unrelated fully matched cord blood transplant, having received weekly enzyme replacement therapy (ERT) prior to transplant. Though an infectious aetiology was clinically suspected to be the cause of her unanticipated acute deterioration and untimely demise, autopsy findings suggested that a combination of pre-existing but sub-clinical Hurler related cardiopulmonary pathology and superimposed transplant related pulmonary venopathy as the basis of her death. This case highlights the limitations of ERT in ameliorating cardiorespiratory disease and the failure of standard pre-transplant investigations to detect significant abnormality related to her underlying condition. It also reinforces the importance of autopsy in explaining unanticipated events.

Competing interests: None declared

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References

  • Aldenhoven M, Boelens JJ, de Koning TJ (2008 May) The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 14(5):485–498

    Article  PubMed  CAS  Google Scholar 

  • Barker CC, Butzner JD, Anderson RA, Brant R, Sauve RS (2003) Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric haematopoietic stem cell transplant recipients. Bone Marrow Transplant 32:79–87

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Braunlin EA, Rose AG, Hopwood JJ, Candel RD, Krivit W (2001) Coronary artery patency following long-term successful engraftment 14 years after bone marrow transplantation in the Hurler syndrome. Am J Cardiol 88:1075–1077

    Article  PubMed  CAS  Google Scholar 

  • Braunlin EA, Stauffer NR, Peters CH et al (2003) Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 92(7):882–886

    Article  PubMed  Google Scholar 

  • Braunlin EA, Harmatz PR, Scarpa M, Furlanetto B, Kampmann C, Rosenfeld HM, Giugliani R (2011 December) Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis 34(6):1183–1197

    Article  PubMed  CAS  Google Scholar 

  • Copell JA, Richardson PG, Soiffer R et al (2010) Hepatic veno-occlusive disease following stem cell transplantation: ncidence, clinical course and outcome. Biol Blood Marrow Transplant 16:157–168

    Article  Google Scholar 

  • Corbacioglu S, Cesaro S, Faraci M, Valteau-Counaet D, Bruhn B et al (2012) Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open label, phase 3, randomized controlled trial. Lancet 379(9823):1301–9

    Google Scholar 

  • Cox-Brinkman J, Boelens JJ, Wraith JE, O’Meara A, Veys P, Wijburg FA, Wulffraat N, Wynn RF (2006) Haematopoietic cell transplantation in combination with enzyme replacement therapy in patients with Hurler syndrome. Bone Marrow Transplant 38:17–21

    Article  PubMed  CAS  Google Scholar 

  • 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 1: results of a European consensus procedure. Orphanet J of Rare Diseases 6(1–9):55

    Google Scholar 

  • Gassas A, Sung L, Doyle JJ, Clarke JTR, Saunders EF (2012) Life threatening pulmonary hemorrhage post bone marrow transplantation in Hurler syndrome. Report of three cases and review of the literature. Bone Marrow Transplant 32:213–215

    Article  Google Scholar 

  • Hirth A, Berg A, Greve G (2007) Successful treatment of severe heart failure in an infant with Hurler syndrome. J Inherit Metabol Dis 30(5):820

    Article  CAS  Google Scholar 

  • Krivit W, Henslee-Downey J, Klemperer M (2005) Survival in Hurler’s disease following bone marrow transplantation in 84 patients. Bone Marrow Transplant 15:S182–S185

    Google Scholar 

  • Leal GN, dePaula AC, Leone C, Kim CA (2010) Echocardiographic study of paediatric patients with mucopolysaccharidosis. Cardiol Young 20:1146–1148

    Article  Google Scholar 

  • Malm G, Gustafsson B, Berglund G et al (2008) Outcome in six children with mucopolysaccharoidosis type 1H, Hurler syndrome, aster haematopoietic stem cell transplantation (HSCT). Acta Paediatr 87:1108–1112

    Article  Google Scholar 

  • Marsden D, Levy H (2010) Newborn screening of lysosomal storage disorders. Clin Chem 56:1071–1079

    Article  PubMed  CAS  Google Scholar 

  • Montani D, O'Callaghan DS, Savale L, Jaïs X, Yaïci A, Maitre S, Dorfmuller P et al (2010 July) Pulmonary veno-occlusive disease: recent progress and current challenges. Respir Med 104(Suppl 1):S23–32, Epub 2010 Apr 24

    Article  PubMed  Google Scholar 

  • Muenzer J, Wraith JE, Clarke LA (2009) Mucopolysaccharoidosis 1: management and treatment guidelines. Pediatrics 123:19–29

    Article  PubMed  Google Scholar 

  • Orchard PJ, Milla C, Braunlin E et al (2010) Pre-transplant risk factors affecting outcome in Hurler syndrome. Bone Marrow Transplant 45:1239–1246

    Article  PubMed  CAS  Google Scholar 

  • Peters C, Steward CG (2003) Haematopoietic stem cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 31:229–239

    Article  PubMed  CAS  Google Scholar 

  • Prasad VK, Tolar J, Wynn RF, Peters C (2010) Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. Pediatr Clin North Am 57(1):123–145

    Article  PubMed  Google Scholar 

  • Vassal G, Koscielny S, Challine D et al (1996) Busulphan disposition and hepatic veno-occlusive disease in children undergoing bone marrow transplantation. Cancer Chemother Pharmacol 37:247–253

    Article  PubMed  CAS  Google Scholar 

  • Wiseman DH, Mercer J, Tylee K, Malaiya N, Bonney DK, Jones SA, Wraith JE, Wynn RF (2012) Management of mucopolysaccharidosis type 1H (Hurler syndrome) presenting in infancy with severe dilated cardiomyopathy: a single institution’s experience. J Inherit Metab Dis. (EPub ahead of print)

    Google Scholar 

  • Yano S, Moseley K, Pavlova Z (2009) Postmortem studies on a patient with mucopolysaccharidosis type 1: Histopathological findings after one year of enzyme replacement therapy. J Inherit Metabol Dis 32(Suppl 1):53–57

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Histopathology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

    Sampada Gupta & Michael McDermott

  2. Department of Oncology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland

    Anne O’Meara

  3. Department of Haematology, Royal Manchester Children’s Hospital, Manchester, UK

    Robert Wynn

Authors
  1. Sampada Gupta
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  2. Anne O’Meara
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  3. Robert Wynn
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  4. Michael McDermott
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Corresponding author

Correspondence to Michael McDermott .

Editor information

Editors and Affiliations

  1. Sektionen für Humangenetik und Klinische, Medizinische Universität Innsbruck, Schöpfstr. 41, Innsbruck, A-6020, Austria

    Johannes Zschocke

  2. Washington State University, Clinical Pharmacology Unit, Division of Health Sciences, E. Spokane Falls Blvd. 412, Spokane, 99210-1495, Washington, USA

    K Michael Gibson

  3. , Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, United Kingdom

    Garry Brown

  4. Medical Center, Department of Pediatrics, Radboud University Nijmegen, Geert Grooteplein 9, Nijmegen, 6500 HB, Netherlands

    Eva Morava

  5. Heidelberg University Hospital, Center for Child and Adolescent Medicine, Im Neuenheimer Feld 430, Heidelberg, 69120, Germany

    Verena Peters

Additional information

Communicated by: Olaf Bodamer

Appendices

Take-Home Message

Standard pre-transplant workup may underestimate the extent of cardiorespiratory disease in Hurler syndrome which may be compounded by current conditioning regimens.

Author Contributions

Sampada Gupta: Specialist registrar in histopathology, assisted with the autopsy examination and wrote the initial draft of the manuscript.

Anne O’Meara: Consultant in paediatric oncology, was responsible for the care of the patient from the time of diagnosis of Hurler syndrome and edited the manuscript.

Robert Wynn: Consultant in paediatric haematology & HSCT, was the transplant physician involved in the patient’s care.

Michael McDermott: Consultant paediatric pathologist, performed the autopsy examination and edited the manuscript.

Guarantor

Dr McDermott serves as guarantor of the article.

Funding

There was no funding associated with this article which is therefore free from any external financial influence.

Ethics and Consent

Ethical approval was not required for this report, but family members have consented to the publication of these findings.

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© 2013 SSIEM and Springer-Verlag Berlin Heidelberg

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Gupta, S., O’Meara, A., Wynn, R., McDermott, M. (2013). Fatal and Unanticipated Cardiorespiratory Disease in a Two-Year-Old Child with Hurler Syndrome Following Successful Stem Cell Transplant. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 10. JIMD Reports, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_213

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  • DOI: https://doi.org/10.1007/8904_2013_213

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-37333-6

  • Online ISBN: 978-3-642-37334-3

  • eBook Packages: MedicineMedicine (R0)

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