title: 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.
authors.affiliation: Department of Paediatric Blood and Marrow Transplant, Royal Manchester Children's Hospital, Oxford Rd, Manchester, M13 9WL, UK.
authors.forename: Su Han
authors.initials: SH
authors.lastname: Lum
authors.affiliation: Mark Holland Metabolic Unit, Adult Inherited Metabolic Disorders, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Karolina M
authors.initials: KM
authors.lastname: Stepien
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester, UK.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Broomfield
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Church
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Mercer
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Jones
authors.affiliation: Department of Paediatric Blood and Marrow Transplant, Royal Manchester Children's Hospital, Oxford Rd, Manchester, M13 9WL, UK. robert.wynn@cmft.nhs.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Wynn
mesh_terms: D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D006331:Heart Diseases / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000209:etiology* / Q000401:mortality; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications* / Q000401:mortality*; D016896:Treatment Outcome