title: 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.affiliation: UMDNJ-Robert Wood Johnson Medical School, Dept. of Neurosurgery, Camden, NJ 08103, USA. janson@memorymatters.org
authors.forename: C G
authors.initials: CG
authors.lastname: Janson
authors.forename: S W J
authors.initials: SW
authors.lastname: McPhee
authors.forename: J
authors.initials: J
authors.lastname: Francis
authors.forename: D
authors.initials: D
authors.lastname: Shera
authors.forename: M
authors.initials: M
authors.lastname: Assadi
authors.forename: A
authors.initials: A
authors.lastname: Freese
authors.forename: P
authors.initials: P
authors.lastname: Hurh
authors.forename: J
authors.initials: J
authors.lastname: Haselgrove
authors.forename: D J
authors.initials: DJ
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Bilaniuk
authors.forename: P
authors.initials: P
authors.lastname: Leone
mesh_terms: 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
chemical_list: D004151:Dipeptides; D011522:Protons; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate