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Journal of Inherited Metabolic Disease

, Volume 40, Issue 3, pp 455–460 | Cite as

Long term survival and cardiopulmonary outcome in children with Hurler syndrome after haematopoietic stem cell transplantation

  • Su Han Lum
  • Karolina M. Stepien
  • Arunabha Ghosh
  • Alexander Broomfield
  • Heather Church
  • Jean Mercer
  • Simon Jones
  • Robert WynnEmail author
Original Article

Abstract

Premature death in untreated children with Hurler syndrome (HS) in the first decade of life is largely due to life-threatening cardiopulmonary complications. We examined the long-term survival and cardiopulmonary outcome in 54 children undergoing haematopoietic stem cell transplantation (HSCT) at the Royal Manchester Children’s Hospital from 1985 to 2008. The median age at first HSCT was 15.1 months. Eighteen had graft failure and nine died after first HSCT. Of 18 patients with graft failure, 17 underwent second HSCT and the remaining one was lost to follow-up (LOF). Twelve were alive-and-engrafted after second HSCT. The overall survival at one year and 20-years was the same at 73.7%. Six children were followed up at the referral centers and excluded from cardiopulmonary endpoint review. Of the 33 evaluable children for the cardiopulmonary endpoints, nine (27.3%) had normal cardiac assessment. Of the four children on angiotensin-converting-enzyme inhibitors, two had mild cardiomyopathy and two had aortic valvular replacement. Twenty (60%) had mild/moderate mitral and/or aortic insufficiencies. Two had overnight hypoxia needing nocturnal non-invasive support. Enzyme level and donor chimerism are important predictors of long-term cardiac outcome.

Keywords

Enzyme Replacement Therapy Haematopoietic Stem Cell Transplantation Donor Chimerism Hurler Syndrome National Health Service Foundation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ACEI

Angiotensin converting enzyme inhibitors

AR

Aortic regurgitation

BBB

Blood-brain barrier

CMV

Cytomegalovirus

CNS

Central nervous system

ERT

Enzyme replacement therapy

EBV

Epstein-Barr virus

GAG

Glycoaminoglycans

HLA

Human leucocyte antigen

HS

Hurler syndrome

HSCT

Haematopoietic stem cell transplantation

LOF

Lost to follow-up

PTLD

Post-transplant lymphoproliferative disease

IDUA

∝-L-iduronidase deficiency

MPS

Mucopolysaccharidosis

MR

Mitral regurgitation

OS

Overall survival

RMCH

Royal Manchester Children’s Hospital

SVT

Supraventricular tachycardia

Notes

Compliance with ethical standards

Conflict of interest

None.

Details of funding

None.

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Copyright information

© SSIEM 2017

Authors and Affiliations

  • Su Han Lum
    • 1
  • Karolina M. Stepien
    • 2
  • Arunabha Ghosh
    • 3
  • Alexander Broomfield
    • 3
  • Heather Church
    • 3
  • Jean Mercer
    • 3
  • Simon Jones
    • 3
  • Robert Wynn
    • 1
    Email author
  1. 1.Department of Paediatric Blood and Marrow TransplantRoyal Manchester Children’s HospitalManchesterUK
  2. 2.Mark Holland Metabolic Unit, Adult Inherited Metabolic DisordersSalford Royal NHS Foundation TrustSalfordUK
  3. 3.Manchester Centre for Genomic MedicineSt. Mary’s HospitalManchesterUK

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