Fabry disease: an ultrastructural comparative study of skin in hemizygous and heterozygous patients
Adult
Male
Heterozygote
Adolescent
Fibroblasts
Middle Aged
Severity of Illness Index
Glycosphingolipids
3. Good health
Microscopy, Electron
03 medical and health sciences
Sex Factors
0302 clinical medicine
alpha-Galactosidase
Fabry Disease
Humans
Female
Lysosomes
Skin
DOI:
10.1007/s00401-005-0026-8
Publication Date:
2006-02-06T18:12:04Z
AUTHORS (9)
ABSTRACT
Fabry disease is a rare X-linked lysosomal storage disorder due to alpha galactosidase A deficiency, better known after the advent of a promising treatment, a periodical enzyme replacement. As other hereditary X-linked disorders, females have historically been considered non-affected carriers, although they are, actually, clinically and pathologically affected to a variable degree. Some women are asymptomatic, but the majority present milder forms of the disease and later onset. This wide range of disease expression is supposed to be related to the levels of enzymatic activity, probably in accordance with a skewing of X inactivation. Lysosomal deposits of ceramide trihexoside have been repeatedly documented in a wide range of tissues, including those found in angiokeratoma, the characteristic cutaneous lesion which allowed the definition of Fabry disease. The aim of this study was to investigate whether there was any difference in the amount of dermal lysosomal storage in males and females, thus accounting for the difference in clinical severity of both groups. For that purpose, with electron microscopy and quantitative methods, we studied the extent of lysosomal deposits in dermal fibroblasts of normal-appearing skin in six females and nine men, enzymatically and genetically proven as to have Fabry disease, and results were compared. Our results indicate a statistically significant difference between the two groups regarding both the percentage of dermal fibroblasts bearing stored material, and the storage surface occupied in 100 fibroblasts per case. We suggest that periodical ultrastructural examination of normal-appearing skin could be an indicator of the efficacy of enzyme replacement therapy and could help to evaluate results.
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