HISTORY AND ADMISSION FINDINGS: A 32-year-old woman with bilateral corneal opacities was at 9 years of age diagnosed to have reduced activity of the enzyme alpha-galactosidase A. She was admitted to our hospital because of skin lesions that had developed over the last 8 years. INVESTIGATIONS: The clinical features included angiokeratomas on the buttocks, hips, and periumbilical region, whorl-like corneal opacity (cornea verticillata), and mitral valve prolapse. Activity of alpha-galactosidase A was reduced to about a quarter of the normal value. Histological examination revealed lipid deposits within the endothelial cells of the skin. Molecular analysis of the alpha-galactosidase A gene revealed a point mutation at nucleotide-position 691 in exon 5 (p.Asp231Asn). TREATMENT AND COURSE: Enzyme replacement therapy with agalsidase alfa 0.2 mg/kg body-weight, infused over 40 min every other week, was initiated. So far no side effects due to the infusion therapy have been noted. The therapeutic success (reduction of lipid storage) cannot be assessed as yet. CONCLUSION: Fabry disease results from deficient activity of the enzyme alpha-galactosidase A. Affected (hemizygous) males often show the complete spectrum of symptoms and signs and have a deficient alpha-galactosidase A activity. Occasionally milder oligosymptomatic courses are observed, when residual enzyme activity is present. In contrast to previous belief, heterozygous females may be affected in the same manner as hemizygotes and may also have a significantly reduced enzyme activity.
