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

[canavan disease]

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 T 1 , 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 .