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

Victor Kovac; Elsa G Shapiro; Kyle D Rudser; Bryon A Mueller; Julie B Eisengart; Kathleen A Delaney; Alia Ahmed; Kelly E King; Brianna D Yund; Morton J Cowan; Julian Raiman; Eva G Mamak; Paul R Harmatz; Suma P Shankar; Nadia Ali; Stephanie R Cagle; Jeffrey R Wozniak; Kelvin O Lim; Paul J Orchard; Chester B Whitley; Igor Nestrasil

doi:10.1016/j.ymgme.2022.01.001

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

Mol Genet Metab. 2022 Feb;135(2):122-132. doi: 10.1016/j.ymgme.2022.01.001. Epub 2022 Jan 7.

Authors

Victor Kovac¹, Elsa G Shapiro², Kyle D Rudser³, Bryon A Mueller⁴, Julie B Eisengart⁵, Kathleen A Delaney⁶, Alia Ahmed⁷, Kelly E King⁸, Brianna D Yund⁹, Morton J Cowan¹⁰, Julian Raiman¹¹, Eva G Mamak¹², Paul R Harmatz¹³, Suma P Shankar¹⁴, Nadia Ali¹⁵, Stephanie R Cagle¹⁶, Jeffrey R Wozniak¹⁷, Kelvin O Lim¹⁸, Paul J Orchard¹⁹, Chester B Whitley²⁰, Igor Nestrasil²¹

Affiliations

¹ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: vjwkovac@gmail.com.
² Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: shapi004@umn.edu.
³ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: rudser@umn.edu.
⁴ Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: muell093@umn.edu.
⁵ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: eisen139@umn.edu.
⁶ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: delan011@umn.edu.
⁷ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: ahmed306@umn.edu.
⁸ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: kingx780@umn.edu.
⁹ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: bdy@umn.edu.
¹⁰ UCSF Benioff Children's Hospital, University of California, San Francisco, CA, USA. Electronic address: mort.cowan@ucsf.edu.
¹¹ Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: julian.raiman@nhs.net.
¹² Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: eva.mamak@sickkids.ca.
¹³ UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA. Electronic address: pharmatz@mail.cho.org.
¹⁴ Department of Ophthalmology and Human Genetics, Emory University, Atlanta, GA, USA. Electronic address: spshankar@ucdavis.edu.
¹⁵ Department of Human Genetics, Emory University, Atlanta, GA, USA. Electronic address: nadia.ali@emory.edu.
¹⁶ Department of Human Genetics, Emory University, Atlanta, GA, USA.
¹⁷ Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: jwozniak@umn.edu.
¹⁸ Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA. Electronic address: kolim@umn.edu.
¹⁹ Division of Pediatric Blood & Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: orcha001@umn.edu.
²⁰ Gene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: whitley@umn.edu.
²¹ Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota, Center for Magnetic Resonance Research (CMRR), Department of Radiology, Minneapolis, MN, USA. Electronic address: nestr007@umn.edu.

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.

Keywords: Brain MRI; Cortex; Hurler Scheie syndrome; Mucopolysaccharidosis; Quantitative brain volumetry; Ventricle.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain / pathology
Humans
Magnetic Resonance Imaging
Mucopolysaccharidosis I* / pathology
Neuroimaging
White Matter* / pathology

Associated data

ClinicalTrials.gov/NCT01870375

Abstract

Publication types

MeSH terms

Associated data

Grants and funding