Janson CG, McPhee SW, Francis J, Shera D, Assadi M, Freese A, Hurh P, Haselgrove J, Wang DJ, Bilaniuk L, Leone P

UMDNJ-Robert Wood Johnson Medical School, Dept. of Neurosurgery, Camden, NJ 08103, USA. janson@memorymatters.org

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.

Mesh Terms:
Age Factors, Aspartic Acid, Atrophy, Brain, Canavan Disease, Case-Control Studies, Child, Preschool, Confidence Intervals, Diffusion Magnetic Resonance Imaging, Dipeptides, Female, Humans, Infant, Magnetic Resonance Spectroscopy, Male, Protons, Reference Values

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