Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I

• Type of Material: Article
• Authors: Victor Kovac, University of Minnesota, Minneapolis; Elsa G Shapiro, University of Minnesota, Minneapolis; Kyle D Rudser, University of Minnesota, Minneapolis; Bryon A Mueller, University of Minnesota, Minneapolis; Julie B Eisengart, University of Minnesota, Minneapolis; Kathleen A Delaney, University of Minnesota, Minneapolis; Alia Ahmed, University of Minnesota, Minneapolis; Kelly E King, University of Minnesota, Minneapolis; Brianna D Yund, University of Minnesota, Minneapolis; Morton J Cowan, University of California San Francisco; Julian Raiman, University of Toronto; Eva G Mamak, Hosp Sick Children; PaulR Harmatz, UCSF Benioff Childrens Hosp Oakland; Suma P Shankar, Emory University; Nadia Ali, Emory University; Stephanie R Cagle, Emory University; Jeffrey R Wozniak, University of Minnesota, Minneapolis; Kelvin O Lim, University of Minnesota, Minneapolis; Paul J Orchard, University of Minnesota, Minneapolis; Chester B Whitley, University of Minnesota, Minneapolis; Igor Nestrasil, University of Minnesota, Minneapolis
• Language: English
• Date: 2022-02-03
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ymgme.2022.01.001
• Title of Journal or Parent Work: MOLECULAR GENETICS AND METABOLISM
• Volume: 135
• Issue: 2
• Start Page: 122
• End Page: 132
• Grant/Funding Information: The study was funded by the Sanofi Genzyme (GZ-2014-11270), the National MPS Society, Million Dollar Bike Ride from the University of Pennsylvania (MDBR-16-125-MPS, 303052MPSI-16-003-02), the Ryan Foundation, the Rare Diseases Clinical Research Network, Lysosomal Disease Network, NIH U54NS065768, and the resources of the Center for Magnetic Resonance Research (supported by NIBIB P41 EB027061, P30 NS076408, and 1S10OD017974-01), the Center for Neurobehavioral Development, and the Minnesota Supercomputing Institute.; 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/Takeda (4-7-year-old 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 UL1TR000004. Its contents are solely the authors’ responsibility and do not necessarily represent the official views of the NIH.
• Keywords: CORPUS-CALLOSUM; Life Sciences & Biomedicine; Ventricle; Cortex; Hurler Scheie syndrome; CORTEX; SEGMENTATION; Endocrinology & Metabolism; THICKNESS; Genetics & Heredity; VOLUME; Research & Experimental Medicine; Science & Technology; Quantitative brain volumetry; Brain MRI; COGNITIVE DECLINE; Medicine, Research & Experimental; DISEASE; HEALTHY-CHILDREN; Mucopolysaccharidosis; ENZYME-REPLACEMENT THERAPY; MPS-I

Abstract

Objective: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. Methods: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4–25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. Results: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4–5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. Conclusions: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.