Objective Previous research suggests attention and white matter (WM) abnormalities in individuals with mucopolysaccharidosis type I (MPS I); this cross-sectional comparison is one of the first to examine the relationship of WM structural abnormalities as measured by corpus callosum (CC) volumes with attention scores to evaluate this relationship in a larger sample of patients with MPS I.MethodsVolumetric MRI data and performance on a computerized measure of sustained attention were compared for 18 participants with the severe form of MPS I (MPS IH), 18 participants with the attenuated form of MPS I (MPS IATT), and 60 typically developing age-matched controls.ResultsThe MPS I groups showed below-average mean attention scores (p < 0.001) and smaller CC volumes (p < 0.001) than controls. No significant associations were found between attention performance and CC volume for controls. Attention was associated with posterior CC volumes in the participants with MPS IH (p = 0.053) and total (p = 0.007) and anterior (p < 0.001) CC volumes in participants with MPS IATT.ConclusionsWe found that attention and CC volumes were reduced in participants with MPS I compared to typically developing controls. Smaller CC volumes in participants with MPS I were associated with decreased attention; such an association was not seen in controls. While hematopoietic cell transplantation used to treat MPS IH may compound these effects, attention difficulties were also seen in the MPS IATT group, suggesting that disease effects contribute substantially to the clinical attentional difficulties seen in this population.
Bibliographical noteFunding Information:
K.E. King is a consultant for Shire Plc; has received research support from Shire, Sanofi Genzyme, and Alexion Pharmaceuticals, Inc; and has had previous contract work for Shapiro Neuropsychology Consulting. K.D. Rudser reports no disclosures relevant to the manuscript. I. Nestrasil is a consultant for Armagen, Biomarin, RegenxBio, ICON, Bioclinica, and Quantims and received research support from Biomarin, Sanofi Genzyme, and Shire. V. Kovac reports no disclosures relevant to the manuscript. K. Delaney is an employee of BioMarin Pharmaceuticals. J.R. Wozniak, B.A. Mueller, and K.O. Lim report no disclosures relevant to the manuscript. J.B. Eisengart reports consulting fees for Regenxbio, Armagen, Sanofi Genzyme, and Velocity; contract work for Shapiro Neuropsychology Consulting; travel support from Regenxbio and the UK MPS Society; and research support with Sangamo and the National MPS Society. E.G. Mamak receives or has received an educational grant from Shire, Biomarin, Gen-zyme, and Actelion; travel grants from Shire; and honoraria from Genzyme and Shire. J. Raiman has received speakers fees and travel support or research support from Shire, Sanofi Genzyme, Biomarin, and Alexion. N. Ali has received research support from Shire, Sanofi Genzyme, BioMarin, Amicus, and Pfizer, as well as lecturers’ honoraria from Sanofi Genzyme, BioMarin, and Amicus. S. Cagle has received speaker and consultant honoraria from BioMarin, Sanofi Genzyme, and Shire. P. Harmatz reports consulting fees from BioMarin, Inventiva, Armagen, PTC, and RegenixBio, as well as consulting fees, travel fees, and honoraria from Chiesi, Shire, Sanofi-Genzyme, and Alexion. C.B. Whitley reports NIH funding, including for the Lysosomal Disease Network (Rare Diseases Clinical Research Network) (NIH U54NS065768). E.G. Shapiro reports consulting fees from Shapiro Neuropsychology Consulting, LLC. Go to Neurology.org/N for full disclosures.
This study was funded by the Genzyme/Sanofi Corp, Rare Diseases Clinical Research Network, Lysosomal Disease Network, NIH U54NS065768, and the resources of the Center for Magnetic Resonance Research and the Center for Neurobehavioral Development. Control data were supported by the NIH (5P41RR008079, 5K12RR023247, P30-NS057091, and MO1-RR00400; K24 MH071434, K24 DA028773, RO1-MH61744, R01-AA12479, and RO1-MH63407 to Master Drug Data Base), Medical Investigation of Neurodevelopmental Disorders Institute, and Gillette Children’s Research Fund, Shire (4-to7-year-olds study), and Clinical and Translational Science Institute grant support (UL1TR000114 from the National Center for Advancing Translational Sciences [NCATS] of the NIH). This publication was also supported in part by the NIH NCATS through UCSF-CTSI grant UL1 TR000004 (Dr. Harmatz). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Study data were collected and managed with REDCap electronic data capture tools hosted at the University of Minnesota. The Lysosomal Disease Network (U54NS065768) is a part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, and NCATS. This consortium is funded through a collaboration between NCATS, the National Institute of Neurological Disorders and Stroke, and the National Institute of Diabetes and Digestive and Kidney Diseases.