Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment

Elsa G. Shapiro, Igor Nestrasil, Kyle Rudser, Kathleen Delaney, Victor Kovac, Alia Ahmed, Brianna Yund, Paul J. Orchard, Julie Eisengart, Gregory R. Niklason, Julian Raiman, Eva Mamak, Morton J. Cowan, Mara Bailey-Olson, Paul Harmatz, Suma P. Shankar, Stephanie Cagle, Nadia Ali, Robert D. Steiner, Jeffrey WozniakKelvin O. Lim, Chester B. Whitley

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Objectives: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden. Methods: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls. Results: Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH. Conclusions: Cognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalMolecular Genetics and Metabolism
Volume116
Issue number1-2
DOIs
StatePublished - Sep 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 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:
This project was supported in part (Dr. Rudser) by the National Center for Advancing Translational Sciences, National Institutes of Health , through University of Minnesota—CTSI Grant Number NCATS UL1TR000114 . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Funding Information:
This project was supported in part (Dr. Harmatz) by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004 . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Keywords

  • Genotypes
  • Mucopolysaccharidosis Type I
  • Neurocognition
  • Neuroimaging

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