Diffuse structural and metabolic brain changes in Fabry disease

J Neurol. 2006 Apr;253(4):434-40. doi: 10.1007/s00415-005-0020-z. Epub 2006 Mar 20.


Objectives: 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.

Design/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Axons / pathology
  • Brain / pathology*
  • Brain Chemistry / physiology*
  • DNA / genetics
  • Disease Progression
  • Fabry Disease / metabolism*
  • Fabry Disease / pathology*
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Mutation / genetics
  • Mutation / physiology
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / metabolism


  • Aspartic Acid
  • DNA
  • N-acetylaspartate
  • alpha-Galactosidase