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

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.

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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

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Correspondence to Robert Wynn.

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Communicated by: Frits Wijburg

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Lum, S.H., Stepien, K.M., Ghosh, A. et al. Long term survival and cardiopulmonary outcome in children with Hurler syndrome after haematopoietic stem cell transplantation. J Inherit Metab Dis 40, 455–460 (2017). https://doi.org/10.1007/s10545-017-0034-6

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Keywords

  • Enzyme Replacement Therapy
  • Haematopoietic Stem Cell Transplantation
  • Donor Chimerism
  • Hurler Syndrome
  • National Health Service Foundation