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.


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