Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI.

Abstract

Canavan disease is a childhood leukodystrophy caused by mutations in the gene for human aspartoacylase ( ASPA), which leads to an abnormal accumulation of the substrate molecule N-acetyl-aspartate (NAA) in the brain. This study was designed to model the natural history of Canavan disease using MRI and proton magnetic resonance spectroscopy ( (1)H-MRS). NAA and various indices of brain structure (morphology, quantitative T1, fractional anisotropy, apparent diffusion coefficient) were measured in white and gray matter regions during the progression of Canavan disease. A mixed-effects statistical model was used to fit all outcome measures. Longitudinal data from 28 Canavan patients were directly compared in each brain region with reference data obtained from normal, age-matched pediatric subjects. The resultant model can be used to non-invasively monitor the natural history of Canavan disease or related leukodystrophies in future studies involving drug, gene therapy, or stem cell treatments.

• Authors: C G Janson, S W J McPhee, J Francis, D Shera, M Assadi, A Freese, P Hurh, J Haselgrove, D J Wang, L Bilaniuk, P Leone
• Journal: Neuropediatrics (Neuropediatrics) Vol. 37 Issue 4 Pg. 209-21 (Aug 2006) ISSN: 0174-304X [Print] Germany
• PMID: 17177147 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dipeptides
• Protons
• isospaglumic acid
• Aspartic Acid
• N-acetylaspartate

Topics

• Age Factors
• Aspartic Acid (analogs & derivatives, metabolism)
• Atrophy
• Brain (pathology)
• Canavan Disease (diagnosis)
• Case-Control Studies
• Child, Preschool
• Confidence Intervals
• Diffusion Magnetic Resonance Imaging (methods)
• Dipeptides (metabolism)
• Female
• Humans
• Infant
• Magnetic Resonance Spectroscopy (methods)
• Male
• Protons
• Reference Values