Renal involvement in Fabry's disease.

Fabry's disease is a sphingolipid storage disorder which is caused by mutations within the gene responsible for the expression of the lysosomal hydrolase, oc-galactosidase A ( 1). The enzyme defect results in the progressive deposition of uncleaved glycosphingolipids within lysosomes of endothelial, perithelial and smooth muscle cells. The major clinical features may be divided into cutaneous lesions (angiokeratoma), ophthalmological abnormalities (corneal dystrophy), neurological abnormalities, cardiovascular diseases and renal involvement. A variety of techniques allowed the structural gene responsible for production of mature a-galactosidase A to be localized to the middle of the long arm of the X chromosome, Xq22 (2). Point mutation within the gene, and partial or complete gene deletions, result in the classical phenotypic expression of the disease. No immunologically detectable or catalytically active enzyme protein is found in these patients. Elucidation of the genomic structure of the a-galactosidase A gene and its organization have facilitated the investigation of the molecular lesions producing these defects. Since most of a-galactosidase A gene mutations have been "private" occuring only in single pedigrees, the accurate identification of specific molecular defects in individual families would be impractical and may not be necessary. The unifying abnormality in all affected tissues is the accumulation of intracellular glycosphingolipid. The most striking renal changes are present in glomeruli, although tubules and blood vessels are also abnormal. Glomerular visceral epithelial cells are enlarged and vacuolated. The vacuoles generally are small and uniform and impart a "honeycomb" appearance to these cells (3-5).