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.
“J.E. Wraith was deceased at the time of publication.”
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Acknowledgment
We would like to acknowledge the assistance of Edward Bendert, Jean Mercer, and Brianna Yund in the completion of this study and extend our gratitude to the families who participated in this research. This study was supported by The Society for Mucopolysaccharide Disease in the United Kingdom and in part by the National MPS Society, the United States (K. Bjoraker). Work on this study by Kyle Rudser was supported by UL1TR000114 from NCATS of NIH.
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Communicated by: Francois Feillet, MD, PhD
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Synopsis
Mutation type (i.e., homozygous for nonsense or deletion mutations or heterozygous for a combination of these) is significantly associated with both cognitive and functional adaptive outcomes post transplant and may have relevance for early identification of children at risk for severe long-term neurocognitive impairment despite treatment.
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The authors declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants included in the study.
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This article does not contain any studies with animal subjects performed by any of the authors.
Details of the Contributions of Individual Authors
A.S. Kunin-Batson, led manuscript writing and scientific conceptualization.
E.G. Shapiro assisted in writing paper and scientific conceptualization and assisted in obtaining Minnesota data.
K.D. Rudser statistical analysis, writing and editing.
C. Lavery scientific conceptualization; IQ, data collection in the United Kingdom, manuscript review and editing.
K.J. Bjoraker scientific conceptualization; data collection in Minnesota, manuscript review and editing.
S. Jones provided medical data and collaborated with Ms. Lavery in getting study accomplished, manuscript review and editing.
R. Wynn provided medical data regarding transplant and participated in manuscript review and editing.
A. Vellodi provided medical data regarding transplant, manuscript review and editing.
J. Tolar provided medical data regarding transplant, manuscript review and editing.
P. Orchard provided medical data regarding transplant, manuscript review and editing.
J.E. Wraith (deceased) collaborated with Ms. Lavery in getting study accomplished.
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Kunin-Batson, A.S. et al. (2015). Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 29. JIMD Reports, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_521
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DOI: https://doi.org/10.1007/8904_2015_521
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