title: Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation.
abstract: The long-term cognitive and functional outcomes of children with mucopolysaccharidosis type I (MPS-IH) post-hematopoietic cell transplant (HCT) are not well documented, and the role of genetic and treatment factors in these outcomes has yet to be defined. In this multi-site, international study, we (1) characterize the cognitive and functional status of 47 individuals (ages 2-25, mean of 10.6 years) with MPS-IH who are 1-24 years post HCT (mean = 9 years) and (2) examine contributions of genotype, transplant characteristics, and sociodemographic factors to cognitive ability, adaptive behavior, and quality of life. The overall cognitive ability of our sample was mildly impaired, more than two standard deviations below general population norms. Parent reported adaptive behaviors (i.e., communication, daily living, and motor skills) were similarly impaired with a relative strength in socialization. Quality of life, as reported by parents, fell more than two standard deviations below population norms for physical functioning; however, psychosocial quality of life (emotional well-being) approximated population norms. In linear regression analysis, adjusted for demographic and treatment factors, mutation severity was associated with lower cognitive ability (p = 0.005) and adaptive functioning (p = 0.004), but not parent ratings of children's quality of life. Older age at HCT was associated with poorer physical quality of life (p = 0.002); lower socioeconomic status (p = 0.028) and unrelated bone marrow HCT (p = 0.010) were associated with poorer psychosocial quality of life. Implications for screening and early intervention for children at risk for poorer cognitive and functional outcomes are described.
authors.affiliation: HealthPartners Institute for Education and Research, Minneapolis, MN, USA.|Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55414, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Kunin-Batson
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55414, USA. shapi004@umn.edu.
authors.forename: E G
authors.initials: EG
authors.lastname: Shapiro
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Rudser
authors.affiliation: Society for Mucopolysaccharide Disease, Buckinghamshire, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Lavery
authors.affiliation: Neuropsychology Consultants, Minneapolis, MN, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Bjoraker
authors.affiliation: Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: R F
authors.initials: RF
authors.lastname: Wynn
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Vellodi
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55414, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55414, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Wraith
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