Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II

Brianna Yund, Kyle Rudser, Alia Ahmed, Victor Kovac, Igor Nestrasil, Julian Raiman, Eva Mamak, Paul Harmatz, Robert Steiner, Heather Lau, Pooja Vekaria, Jeffrey R Wozniak, Kelvin O Lim, Kathleen Delaney, Chester B Whitley, Elsa G Shapiro

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32 Scopus citations


The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild behavior and cognitive impairment that might impact long-term functional outcomes is unknown. Previously, significant MRI abnormalities have been found in MPS II. Recent evidence suggests white matter abnormalities in many MPS disorders. Methods: As the initial cross-sectional analysis of a longitudinal study, we studied the association of brain volumes and somatic disease burden with neuropsychological outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8. MRI volumes were compared to 55 normal controls. Results: While IQ and memory were average, measures of attention were one standard deviation below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes. Conclusions: Despite average intelligence, attention is compromised in attenuated MPS II. Results confirm an important role of corpus callosum and cortical white matter abnormality in MPS II as well as the somatic disease burden in contributing to attention difficulties. Awareness by the patient and caregivers with appropriate management and symptomatic support will benefit the attenuated MPS II patient.

Original languageEnglish (US)
Pages (from-to)170-177
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 1 2015

Bibliographical note

Funding Information:
The Lysosomal Disease Network supported this study through “Longitudinal Studies of Brain Structure and Function in the Mucopolysaccharidoses” (E. Shapiro, P.I.). The Lysosomal Disease Network (U54NS065768) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH (C. Whitley P.I.;).

Funding Information:
Shire supported this study as an investigator initiated research grant (E Shapiro, P.I.).

Funding Information:
This project was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health , through UCSF-CTSI grant number UL1 TR000004 (P. Harmatz) and UMN-CTSI grant number UL1 TR000114 (K. Rudser). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Funding Information:
Support for imaging controls: NIH 5K12RR023247, J Wozniak, P.I.; NIH 5P41RR008079, 5R01MH060662, P30-NS057091, and M01-RR00400 K Lim, P.I.; “Brain Structure and Function in Developmentally Normal Children Ages 4–7”: supported by:


  • Attenuated
  • MRI brain volumes
  • Mucopolysaccharidosis type II
  • Neuropsychological outcomes


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