Natural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI.
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.
Janson
C G
CG
UMDNJ-Robert Wood Johnson Medical School, Dept. of Neurosurgery, Camden, NJ 08103, USA. janson@memorymatters.org
McPhee
S W J
SW
Francis
J
J
Shera
D
D
Assadi
M
M
Freese
A
A
Hurh
P
P
Haselgrove
J
J
Wang
D J
DJ
Bilaniuk
L
L
Leone
P
P
D000367:Age Factors; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D017825:Canavan Disease / Q000175:diagnosis*; D016022:Case-Control Studies; D002675:Child, Preschool; D016001:Confidence Intervals; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004151:Dipeptides / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011522:Protons; D012016:Reference Values
D004151:Dipeptides; D011522:Protons; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate