Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Loss of electron-dense lamellar material from Fabry's disease fibroblasts after enzyme replacement

  • 40 Accesses

  • 6 Citations


Cultured fibroblasts from a patient with Fabry's disease were treated with alpha-galactosidase A. The cells internalized the enzyme via a receptor-mediated transport system, resulting in the uptake of enzyme to 50% of the activity of normal cells. Following uptake of the enzyme and incubation for 9 days, a loss of electron-dense lamellar material within membrane-bound residual bodies was detected by electron microscopy. Morphometric analysis of electron micrographs showed that the percentage volume of cytoplasm occupied by electron-dense lamellar material in Fabry's disease fibroblasts decreased to near normal after treatment with enzyme. These results indicate that the ultrastructural abnormalities of Fabry's disease cells can be corrected by enzyme replacement, at least in cultured fibroblasts.

This is a preview of subscription content, log in to check access.


  1. Beutler E, Kuhl W (1972) Purification and properties of human alpha-galactosidases. J Biol Chem 247:7195–7200

  2. Brady RO, Tallman JF, Johnson WG, Gal AE, Leaky WR, Quirk JM, Dekaban AS (1973) Replacement therapy for inherited enzyme deficiency: Use of purified ceramidetrihexosidase in Fabry's disease. N Engl J Med 289:9–14

  3. Dawson G, Matalon R, Dorfman A (1972) Glycosphingolipids in cultured skin fibroblasts II. Characterization and metabolism in fibroblasts from patients with inborn errors of glycosphingolipid and mucopolysaccharide metabolism. J Biol Chem 247:5951–5958

  4. Dawson G, Matalon R, Li YT (1973) Correction of the enzymatic defect in cultured fibroblasts from patients with Fabry's disease: Treatment with purified alpha-galactosidase from ficin. Pediatr Res 7:684–690

  5. Desnick RJ, Sweeley CC (1983) Fabry's disease: alpha-galactosidase A deficiency. In: Stanbury JB, Wyngaarden JB, Fredrickson, DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 906–944

  6. Desnick RJ, Dean KJ, Grabowski G, Bishop DF, Sweeley CC (1979) Enzyme therapy in Fabry's disease: Differential in vivo plasma clearance and metabolic effectiveness of plasma and splenic alpha-galcatosidase A isozymes. Proc Natl Acad Sci USA 76:5329–5330

  7. Dooley KC, Applegarth DA (1980) Uptake of lysosomal enzymes by human fibroblasts: Lack, of uptake of fungal or plant glycosidases in comparison with a mammalian enzyme. J Inher Metab Dis 3:145–147

  8. Elias H, Hyde DM (1980) An elementary introduction to stereology (quantitative microscopy). Am J Anat 159:412–446

  9. Grabowski GA, Desnick RJ (1981) Enzyme replacement in genetic diseases. In: Holcenberg JS, Roberts J (eds) Enzymes as drugs. John Wiley and Sons, New York, pp 167–208

  10. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

  11. Mayes JS, Beutler E (1977) Alpha-galactosidase A from human placenta: Stability and subunit size. Biochim Biophys Acta 484:408–416

  12. Mayes JS, Scheerer JB, Sifers RN, Donaldson ML (1981) Differential assay for lysosomal alpha-galactosidases in human tissues and its application to Fabry's disease. Clin Chim Acta 112:247–251

  13. Mayes JS, Cray EL, Dell VA, Scheerer JB, Sifers RN (1982) Endocytosis of lysosomal alpha-galactosidase A by cultured fibroblasts from patients with Fabry disease. Am J Hum Genet 34:602–610

  14. McLean J, Stewart G (1974) Fabry's disease: Specific inclusions found on electron microscopy of fibroblast cultures. J Med Genet 11:133–135

  15. Sly WS, Natowicz Gonzalez-Noriega A, Grubb JH, Fischer HD (1981) The role of the mannose-6-phosphate recognition marker and its receptor in the uptake and intracellular transport of lysosomal enzymes. In: Callahan JW, Lowden JA (eds) Lysosomes and lysosomal storage diseases. Raven press, New York, pp 131–146

  16. Yuasa T, Fukama M, Takashima S, Takaki R (1980) Cultured skin fibroblasts in lipidoses. Arch Pathol Lab Med 104:321–327

Download references

Author information

Correspondence to J. S. Mayes.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sifers, R.N., Mayes, J.S. & Nordquist, R.E. Loss of electron-dense lamellar material from Fabry's disease fibroblasts after enzyme replacement. Hum Genet 65, 85–87 (1983). https://doi.org/10.1007/BF00285037

Download citation


  • Electron Microscopy
  • Internal Medicine
  • Metabolic Disease
  • Normal Cell
  • Transport System