Acta Neuropathologica

, Volume 33, Issue 1, pp 9–21 | Cite as

Fabry's disease on the mechanism of the peripheral nerve involvement

  • Nobuyoshi Fukuhara
  • Masahiko Suzuki
  • Nagahisa Fujita
  • Tadao Tsubaki
Original Investigations


A sural nerve biopsy of a patient with Fabry's disease showed depletion of larger myelinated fibres, but smaller myelinated and unmyelinated fibres were intact. Epineurial and to a lesser degree endoneurial vessels revealed abundant lamellar inclusions in the endothelial and perithelial cells. Larger myelinated nerve fibres contained glycogen granules in the vacuoles caused by splitting of the adaxonal membranes. A skin biopsy revealed abundant inclusions in the secretory cells and myoepithelial cells of the sweat glands. The lumen of the gland was packed with inclusions like those in the vessel walls. The pain and anhydrosis might be caused by accumulation of glycolipid in the vasa nervorum and sweat glands and not by autonomic nerve involvement.

Key words

Fabry's Disease Glycolipid Anhydrosis Pain Ultrastructure 


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  1. Aleu, F. P., Terry, R. D., Zellweger, H.: Electron microscopy of two cerebral biopsies in gargoylism. J. Neuropath. exp. Neurol.24, 304–317 (1965)Google Scholar
  2. Bischoff, A., Fierz, U., Ulrich, J.: Peripher-neurologische Störungen bei der Fabryschen Krankheit (Angiokeratoma corporis diffusum universale); Klinische-elektronen-mikroskopische Befunde bei einem Fall. Klin. Wschr.46, 666–671 (1968)Google Scholar
  3. Clarke, J. T. R., Knaack, J., Crawhall, J. C.: Ceramide trihexosidosis (Fabry's disease) without skin lesions. New Engl. J. Med.284, 233–235 (1971)Google Scholar
  4. Comings, D. E., Amromin, G. D.: Autosomal dominant insensitivity to pain with hyperplastic myelinopathy and autosomal dominant indifference to pain. Neurology (Minneap.)24, 838–848 (1974)Google Scholar
  5. De Groot, W. P.: Angiokeratoma corporis diffusum Fabry. Dermatologica (Basel)128, 321–349 (1964)Google Scholar
  6. Desnick, R. J., Sweeley, C. C., Krivit, W.: A method for the quantitative determination of neutral glycosphingolipids in urine sediment. J. Lipid Res.11, 31–37 (1970)Google Scholar
  7. Dyck, P. J., Gutrecht, J. A., Bastron, J. A., Karnes, W. E., Dale, A. J. D.: Histologic and teased-fiber measurements of sural nerve in disorder of lower motor and primary sensory neurons. Proc. Mayo Clin.43, 81–123 (1968)Google Scholar
  8. Ellis, R. A.: Fine structure of the myoepithelim of the eccrine sweat glands of man. J. Cell Biol.27, 551–563 (1965)Google Scholar
  9. Fabry, J.: Ein Beitrag zur Kenntnis der Purpura haemorrhagica nodularis. Arch. Derm. Syph.43, 187–200 (1898)Google Scholar
  10. Fox, J. L.: Development of recent thought on intracranial pressure and blood-brain barrier. J. Neurosurg.21, 909–946 (1964)Google Scholar
  11. Frost, P., Tanaka, Y., Spaeth, G. L.: Fabry's disease—glicolipid lipidosis. Histochemical and electron microscopic studies of two cases. Amer. J. Med.40, 618–627 (1966)Google Scholar
  12. Fukuhara, N., Tsubaki, T.: Increased vascular permeability in the peripheral nerves of rats intoxicated with methyl mercury. Clin. Neurol. (Tokyo)14, 604–612 (1974)Google Scholar
  13. Gemmingen, G., Kierland, R. R., Opitz, J. M.: Angiokeratoma corporis diffusum (Fabry's disease). Arch. Derm.91, 206–218 (1965)Google Scholar
  14. Grunnet, M. L., Spilsbury, P. R.: The central nervous system in Fabry's disease. An ultrastructural study. Arch. Neurol. (Chic.)28, 231–234 (1973)Google Scholar
  15. Ito, T., Shibasaki, S.: Electron microscopic study on human eccrine sweat glands. Arch. Histol. Jap.27, 81–115 (1966)Google Scholar
  16. Jansen, E.: On the pathology of angiokeratoma corporis diffusum (Fabry). Acta path. microbiol. scand.68, 313–331 (1966)Google Scholar
  17. Kahn, P.: Anderson-Fabry disease; A histopathological study of three cases with observations on the mechanism of production of pain. J. Neurol. Neurosurg. Psychiat.36, 1053–1062 (1973)Google Scholar
  18. Kint, J. A.: Fabry's disease; alpha-galactosidase deficiency. Science167, 1268–1269 (1970)Google Scholar
  19. Kocen, R. S., Thomas, P. K.: Peripheral nerve involvement in Fabry's disease. Arch. Neurol. (Chic.)22, 81–88 (1970)Google Scholar
  20. Lou, H. O. C., Reske-Nielsen, E.: The central nervous system in Fabry's disease. A clinical, pathological, and biochemical investigation. Arch. Neurol. (Chic.)25, 351–359 (1971)Google Scholar
  21. Melzack, R., Wall, P. D.: Pain mechanisms: A new theory. Science150, 971–979 (1965)Google Scholar
  22. Miyatake, T.: Fabry's disease. Neurology Topic (Tokyo)1, 25–36 (1971) (Japanese)Google Scholar
  23. Ohnishi, A., Tabira, T., Goto, I., Kuroiwa, Y.: Morphological studies of the sural nerve in a case of Fabry's disease. Brain Nerve (Tokyo)26, 225–231 (1974)Google Scholar
  24. Ohnishi, A., Dyck, P. J.: Loss of small peripheral sensory neurons in Fabry disease. Histologic and morphometric evaluation of cutaneous nerves, spinal ganglia, and posterior columns. Arch. Neurol. (Chic.)31, 120–127 (1974)Google Scholar
  25. Olsson, Y.: Studies on vascular permeability of the peripheral nerves. 1. Distribution of circulating fluorescent serum albumin in normal, crushed and sectioned peripheral nerve. Acta neuropath. (Berl.)7, 1–15 (1966)Google Scholar
  26. Olsson, Y.: Studies on vascular permeability in peripheral nerves. Acta neuropath. (Berl.)17, 114–126 (1971)Google Scholar
  27. Rahman, A. N., Lindenberg, R.: The neuropathology of hereditary dystopic lipidosis. Arch. Neurol. (Chic.)9, 373–385 (1963)Google Scholar
  28. Roth, J., Schulze, E., Raabe, G., Waldmann, G.: Analytische Studie des Morbus Fabry. Virchows Arch., Abt. A, Path. Anat.363, 287–301 (1974)Google Scholar
  29. Scriba, K.: Zur Pathogenese des Angiokeratoma corporis diffusum Fabry mit kardiovasorenalem Symptomen-Komplex. Verh. dtsch. Path. Ges.34, 221–226 (1951)Google Scholar
  30. Steward, V. W., Hitchcock, C.: Fabry's disease (Angiokeratoma corporis diffusum); A report of 5 cases with pain in the extremities as the chief symptom. Path. Europ.3, 377–388 (1968)Google Scholar
  31. Sung, J. H., Hayano, M., Mastri, A. R., Desnick, R.: Neuropathology of Fabry's disease. Abst. 7th Int. Congr. Neuropath., pp. 290. Budapest: Akademiai Kiado 1974Google Scholar
  32. Tabira, T., Goto, I., Kuroiwa, Y., Kikuchi, M.: Neuropathological and biochemical studies in Fabry's disease. Acta neuropath. (Berl.)30, 345–354 (1974)Google Scholar
  33. Takahashi, K.: A clinico-pathologic study on the peripheral nervous system of the aged. I. With special reference to the sciatic nerves. Clin. Neurol. (Tokyo)3, 137–144 (1963)Google Scholar
  34. Volk, B. W., Schneck, L., Cleemons, J. E., Niscastri, A.: Fabry's disease in a black man without skin lesions. Neurology (Minneap.)24, 991–1000 (1974)Google Scholar
  35. Waksman, B. H.: Experimental study of diphtheric polyneuritis in the rabbit and guinea pig. III. The blood-nerve barrier in the rabbit. J. Neuropath. exp. Neurol.20, 35–77 (1961)Google Scholar
  36. Wise, D., Wallace, H. J., Jellinek, E. H.: Angiokeratoma corporis diffusum; A clinical study of eight affected families. Quart. J. Med., new series31, 177–206 (1962)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Nobuyoshi Fukuhara
    • 1
  • Masahiko Suzuki
    • 1
  • Nagahisa Fujita
    • 1
  • Tadao Tsubaki
    • 1
  1. 1.Department of Neurology, Brain Research InstituteNiigata UniversityNiigataJapan

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