An exploratory study of brain function and structure in Mucopolysaccharidosis Type I: Long term observations following hematopoietic cell transplantation (HCT)

• Authors: Elsa Shapiro, University of Minnesota; O. Evren Guler, University of Minnesota; Kyle Rudser, University of Minnesota; Kathleen Delaney, University of Minnesota; Kendra Bjoraker, University of Minnesota; Chester Whitley, University of Minnesota; Jakub Tolar, University of Minnesota; Paul Orchard, University of Minnesota; James Provenzale, Emory University; Kathleen Thomas, University of Minnesota
• Journal Title: Molecular Genetics and Metabolism
• Volume: Volume 107, Number 1-2
• Publisher: Elsevier: 12 months | 2012-09, Pages 116-121
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.ymgme.2012.07.016
• Subjects: Biology, Biostatistics; Biology, Genetics; Health Sciences, Radiology
• Keywords: MPS I; hematopoietic cell transplant; attention span; cognition; diffusion tensor imaging; medical history

Abstract

Aim Although hematopoietic cell transplantation (HCT) arrests the cognitive decline in mucopolysaccharidosis type IH (Hurler syndrome, MPS IH), these children continue to have neuropsychological deficits as they age. Both compromised attention and effects on white matter have been observed in cancer patients who have had chemotherapy. Therefore, we explored the effects of disease and treatment on brain function in children with MPS I who have had HCT with those with attenuated MPS I treated with enzyme replacement therapy (ERT). Methods Subjects: 7 MPS IH participants at least 5 years post-HCT were compared with 7 attenuated participants who were treated with ERT. Measures: IQ, attention, spatial ability, and memory were assessed. Medical history and an unsedated MRI scan using diffusion tensor imaging (DTI) were acquired. Results Despite clinically equivalent IQ and memory, children with MPS IH had poorer attention span than those with attenuated MPS I as well as decreased fractional anisotropy (FA) of the corpus callosum. A relationship between attention scores and FA was found in the MPS IH group but not the attenuated group. FA was also related to frequency of medical events. Interpretation In children with MPS IH, both the treatment and the disease affect attention functions associated with poor white matter integrity.