Diffuse structural and metabolic brain changes in Fabry disease.
OBJECTIVE
To assess structural and metabolic brain changes in subjects affected by Fabry disease (FD) or carrying the disease mutation.


BACKGROUND
FD is an X-linked metabolic disorder due to alpha-galactosidase A deficiency, which leads to storage of glycosphingolipids in many tissues and organs. Previous MR studies have shown structural and metabolic brain abnormalities in FD patients. It is not clear, however, whether tissue damage can be seen in both the brains of hemizygous and heterozygous and whether quantitative MR metrics are useful to monitor disease evolution.


METHODS
We studied 4 males and 4 females with FD. Each subject underwent brain proton MRI/MR spectroscopic imaging (MRSI) examinations to obtain measures of total brain volumes, total brain lesion volumes, magnetization transfer ratios (MTr) in WM and central brain levels of N-acetylaspartate (NAA) to creatine (Cr). A second MR examination was performed in five subjects after 2 years.


RESULTS
Focal WM lesions were found in 2 males and 1 female. The MTr values were always low in the WM lesions of FD subjects (p < 0.001) and also were low in the normal-appearing WM of 2 affected males. Total brain volumes were never decreased in FD subjects. Brain NAA/Cr values were significantly (p = 0.005) lower in FD subjects than in normal controls and correlated closely with Rankin scale measures (r = -0.79). On follow-up examinations, no significant MR changes were found. However, the small changes in NAA/Cr correlated closely with changes in Rankin scores (r = -0.86).


CONCLUSIONS
Subtle structural and metabolic tissue damage can extend beyond WM lesions in FD subjects. Diffuse brain NAA/Cr decrease can be found in FD subjects in relation to the degree of their CNS involvement and its evolution over time.
Marino
Silvia
S
Centro Studi Neurolesi, Medical School University of Messina, Italy.
Borsini
Walter
W
Buchner
Susanna
S
Mortilla
Marzia
M
Stromillo
Maria L
ML
Battaglini
Marco
M
Giorgio
Antonio
A
Bramanti
Placido
P
Federico
Antonio
A
De Stefano
Nicola
N
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology*; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D000795:Fabry Disease / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D000519:alpha-Galactosidase / Q000235:genetics / Q000378:metabolism
D001224:Aspartic Acid; D004247:DNA; C000179:N-acetylaspartate; D000519:alpha-Galactosidase