Journal of Inherited Metabolic Disease

, Volume 33, Supplement 3, pp 395–399

Quantitative in vivo brain magnetic resonance spectroscopic monitoring of neurological involvement in mucopolysaccharidosis type II (Hunter Syndrome)

  • James E. Davison
  • Christian J. Hendriksz
  • Yu Sun
  • Nigel P. Davies
  • Paul Gissen
  • Andrew C. Peet
Research Report

DOI: 10.1007/s10545-010-9197-0

Cite this article as:
Davison, J.E., Hendriksz, C.J., Sun, Y. et al. J Inherit Metab Dis (2010) 33(Suppl 3): 395. doi:10.1007/s10545-010-9197-0

Abstract

Neurological involvement in X-linked mucopolysaccharidosis type II (Hunter syndrome) is indicative of more severe disease, but is not attenuated by current enzyme replacement therapy which does not significantly penetrate the blood–brain barrier. Magnetic resonance spectroscopy is an objective method of determining brain metabolites and has the potential to identify disease biomarkers with utility in evaluating current and novel therapies. MRS studies from seven patients with MPSII all receiving enzyme replacement therapy were compared with a large cohort of children with various neurocognitive disorders with normal MR imaging. All studies were completed on 1.5Tesla clinical MR scanners. Brain metabolite concentrations were determined from basal ganglia and parieto-occipital white matter using LCModel quantification. Serial trends in brain metabolites were analysed. Examination of mean spectra and quantitative metabolite concentrations demonstrated significantly decreased white matter N-acetylaspartate (a neuronal marker), total choline and glutamate, and elevated myo-inositol (glial marker) in MPSII patients. Analysis of serial determinations of white matter N-acetylaspartate demonstrated no change in two patients with stable MR imaging features but decreasing N-acetylaspartate in two patients more severely affected or deteriorating. These data demonstrate the utility of MRS to monitor serial alterations in brain metabolites including N-acetylaspartate which could be used as biomarkers of progressive neurological disease in MPSII. Integrated as an adjunct to MRI, such an approach could aid the evaluation of the efficacy of current ERT and also novel CNS-targeted therapies in MPSII.

Abbreviations

MPSII

Mucopolysaccharidosis Type II

CNS

Central nervous system

ERT

Enzyme replacement therapy

MRS

Magnetic resonance spectroscopy

tNAA

Total N-acetylaspartate

Ins

Myo-inositol

GABA

Gamma-amino-butyric acid

MRI

Magnetic resonance imaging

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • James E. Davison
    • 1
    • 2
    • 5
  • Christian J. Hendriksz
    • 1
  • Yu Sun
    • 3
    • 4
  • Nigel P. Davies
    • 3
    • 4
  • Paul Gissen
    • 1
    • 2
  • Andrew C. Peet
    • 3
    • 4
  1. 1.Clinical Inherited Metabolic DisordersBirmingham Children’s Hospital NHS Foundation TrustBirminghamUK
  2. 2.Clinical & Experimental Medicine, College of Medical & Dental SciencesUniversity of BirminghamBirminghamUK
  3. 3.Cancer Sciences, College of Medical & Dental SciencesUniversity of BirminghamBirminghamUK
  4. 4.Birmingham Children’s Hospital NHS Foundation TrustBirminghamUK
  5. 5.Institute of Child HealthBirmingham Children’s Hospital NHS Foundation TrustBirminghamUK

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