Diffuse structural and metabolic brain changes in Fabry disease.

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.

[Fabry disease in Italy: first epidemiologic and collaborative study]. / Primo studio epidemiologico e collaborativo italiano sulla malattia di Fabry.

The authors sought to define the prevalence of Fabry disease and to establish the incidence and its natural history in Italy. The aim of this study was to point out the first clinical signs and symptoms to perform an early diagnosis and hence to start a specific therapeutic treatment. Fabry disease is an inborn error of metabolism caused by the deficiency of the lysosomal enzyme alpha-galactosidase A. Fabry disease is a severe X-linked disorder presenting with a higher morbidity between the third and the fourth decade of life. Fabry disease may be confused with other diseases or completely misdiagnosed: its frequency is estimated worldwide to be 1:117000. In Italy, 65 patients have been identified by several specialized institutions; age, sex, onset of first clinical signs and symptoms were analyzed and reported. In conclusion, this is the first Italian collaborative study that allows to delineate and point out the clinical signs of Fabry disease to perform a correct and early diagnosis. Enzyme replacement therapy is now available and its early beginning can prevent renal and cardiac failure, improve the quality of life and life expectancy in these patients.