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 Shankar, Stephanie Cagle, Nadia Ali, Robert D. Steiner, Jeffrey WozniakKelvin O. Lim, Chester B. Whitley

Research output: Contribution to journalArticle

33 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 - Jan 1 2015
Externally publishedYes

Keywords

  • Genotypes
  • Mucopolysaccharidosis Type I
  • Neurocognition
  • Neuroimaging

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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    Shapiro, E. G., Nestrasil, I., Rudser, K., Delaney, K., Kovac, V., Ahmed, A., Yund, B., Orchard, P. J., Eisengart, J., Niklason, G. R., Raiman, J., Mamak, E., Cowan, M. J., Bailey-Olson, M., Harmatz, P., Shankar, S., Cagle, S., Ali, N., Steiner, R. D., ... Whitley, C. B. (2015). Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment. Molecular Genetics and Metabolism, 116(1-2), 61-68. https://doi.org/10.1016/j.ymgme.2015.06.002