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Infantile neuroaxonal dystrophy associated with α-N-acetylgalactosaminidase deficiency: on relating axonal spheroids to a lysosomal enzyme deficiency

  • D. Wolfe
Conference paper

Summary

Appropriately for a symposium on peripheral neuropathy, this contribution considers the pathogenesis of distal axonal spheroids in two brothers with biopsy-proven infantile neuroaxonal dystrophy (INAD), who also have a well-delineated inherited defect in lysosomal glycoprotein degradation: α-N-acetylgalactosaminidase deficiency. The possibility that the membranous content of their distal axonal spheroids directly represents the storage product of their lysosomal enzymatic defect is considered. The occurrence of ultra-structurally identical membranous spheroids in inherited and acquired human and experimental diseases unrelated to this lysosomal defect, current knowledge of neuronal lysosomes and of the synthesis, axonal transport, and degradation of glycoproteins in neurons, and the absence of this lysosomal enzymatic defect in cells from unrelated autopsy-proven cases of INAD, all suggest that the axonal spheroids in these brothers either are related to their lysosomal deficiency by highly indirect and undemonstrated paths, or that their membranous axonal spheroids are unrelated causally to their lysosomal deficiency and that ultrastructural storage in this new lysosomal disease remains to be demonstrated by more sensitive and specific methods.

Keywords

Fabry Disease Sural Nerve Biopsy Retrograde Axonal Transport Diabetic Autonomic Neuropathy Axonal Spheroid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Van Diggelen OP, Schindler D, Willemsen R, Boer M, Kleijer WJ, Huijmans JGM, Blom W, Galjaard H (1988) α-N-acetylgalactosaminidase deficiency, a new lysosomal storage disorder. J Inherit Metab Dis 11: 349–357PubMedCrossRefGoogle Scholar
  2. 2.
    Schindler D, Bishop DF, Wolfe DE, Wang AM, Egge H, Lemieux RU, Desnick RJ (1989) Neuroaxonal dystrophy due to lysosomal α-N-acetylgalactosaminidase deficiency. N Engl J Med 320: 1735–1740PubMedCrossRefGoogle Scholar
  3. 3.
    Desnick RJ, Bishop DF (1989) Fabry disease: α-galactosidase deficiency; Schindler disease: α-N-acetylgalactosaminidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, et al (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill: New York, pp 1751–1798Google Scholar
  4. 4.
    Wolfe DE, Schindler D, Desnick RJ, Perl D (1989) Infantile neuroaxonal dystrophy (INAD) associated with a lysosomal enzyme deficiency. J Neuropathol Exp Neurol 48: 349CrossRefGoogle Scholar
  5. 5.
    Peters A, Palay S, Webster HdeF (1991) The fine structure of the nervous system, 3rd edn. Saunders: PhiladelphiaGoogle Scholar
  6. 6.
    Kamoshita S, Neustein HB, Landing BH (1968) Infantile neuroaxonal dystrophy with neonatal onset. Neuropathologic and electron microscopic observations. J Neuropathol Exp Neurol 27: 300–323PubMedCrossRefGoogle Scholar
  7. 7.
    Berard-Badier M, Toga M, Gambarelli D, Hassoun J, Pellissier JF, Pinsard N, Bernard R (1974) Infantile neuroaxonal dystrophy or Seitelberger’s disease. IV. Autonomic nervous system involvement: electron microscopic study in two siblings. Acta Neuropathol 28: 261–267PubMedCrossRefGoogle Scholar
  8. 8.
    Goebel HH, Kohlschutter A, Schulte FJ (1980) Rectal biopsy findings in infantile neuroaxonal dystrophy. Neuropediatrics 11: 388–392PubMedCrossRefGoogle Scholar
  9. 9.
    Schmidt RE, Plurad SB (1986) Ultrastructural and biochemical characterization of autonomic neuropathy in rats with chronic streptozotocin diabetes. J Neuropathol Exp Neurol 45: 525–544PubMedCrossRefGoogle Scholar
  10. 10.
    Yagihashi S, Sima AAF (1986) Diabetic autonomic neuropathy in the BB rat. Ultra-structural and morphometric changes in parasympathetic nerves. Diabetes 35: 733–743PubMedCrossRefGoogle Scholar
  11. 11.
    Schmidt RE, Plurad DA, Plurad SB, Cogswell BE, Diani AR, Roth KA (1989) Ultra-structural and immunohistochemical characterization of autonomic neuropathy in genetically diabetic Chinese hamsters. Lab Invest 61: 77–92PubMedGoogle Scholar
  12. 12.
    Yagihashi S, Sima AAF (1988) Diabetic autonomic neuropathy in the BB rat. Frontiers in diabetes research: lessons from animal diabetes II: 477–481Google Scholar
  13. 13.
    Yagihashi S, Sima AAF (1986) Neuroaxonal and dendritic dystrophy in diabetic autonomic neuropathy. Classification and topographic distribution in the BB-rat. J Neuropathol Exp Neurol 45: 545–565PubMedCrossRefGoogle Scholar
  14. 14.
    Spencer PS, Schaumburg HH (1976) Central-peripheral distal axonopathy — the pathology of dying-back polyneuropathies. Prog Neuropathol 3: 253–295Google Scholar
  15. 15.
    Prineas J (1969) The pathogenesis of dying-back polyneuropathies. Part I. An ultra-structural study of experimental triorthocresyl phosphate intoxication in the cat. J Neuropathol Exp Neurol 28: 571–597PubMedCrossRefGoogle Scholar
  16. 16.
    Bouldin TW, Cavanagh JB (1979) Organophosphorus neuropathy. II. A fine-structural study of the early stages of axonal degeneration. Am J Pathol 94: 253–270PubMedGoogle Scholar
  17. 17.
    Blakemore WF, Cavanagh JB (1969) “Neuroaxonal dystrophy” occurring in an experimental “dying-back” process in the rat. Brain 92: 789–804PubMedCrossRefGoogle Scholar
  18. 18.
    Schaumburg HH, Wisniewski HM, Spencer PS (1974) Ultrastructural studies of the dying-back process. I. Peripheral nerve terminal and axon degeneration in systemic acrylamide intoxication. J Neuropathol Exp Neurol 33: 260–284PubMedCrossRefGoogle Scholar
  19. 19.
    Sahenk Z, Mendell JR (1979) Ultrastructural study of zinc pyridinethione-induced peripheral neuropathy. J Neuropathol Exp Neurol 38: 532–550PubMedCrossRefGoogle Scholar
  20. 20.
    Martin JJ, Martin L (1972) Infantile neuroaxonal dystrophy: ultrastructural study of the peripheral nerves and of the motor end plates. Eur Neurol 8: 239–250PubMedCrossRefGoogle Scholar
  21. 21.
    Shimono M, Ohta M, Asada M, Kuroiwa J (1976) Infantile neuroaxonal dystrophy. Ultrastructural study of peripheral nerve. Acta Neuropathol 36: 71–79PubMedCrossRefGoogle Scholar
  22. 22.
    Williamson K, Sima AAF, Curry B, Ludwin SK (1982) Neuroaxonal dystrophy in young adults: a clinicopathological study of two unrelated cases. Ann Neurol 11: 335–343PubMedCrossRefGoogle Scholar
  23. 23.
    Toga M, Berard-Bodier M, Gambarelli-Dubois D (1970) La dystrophic neuroaxonale infantile ou maladie de Seitelberger. Etude clinique, histologique et ultrastructurale de deux observations. Acta Neuropathol 15: 327–350PubMedCrossRefGoogle Scholar
  24. 24.
    Aicardi J, Castelein P (1979) Infantile neuroaxonal dystrophy. Brain 102: 727–748PubMedCrossRefGoogle Scholar
  25. 25.
    Yagihashi S, Sima AAF (1985) Diabetic autonomic neuropathy in the BB rat. Ultra-structural and morphometric changes in sympathetic nerves. Diabetes 34: 558–564PubMedCrossRefGoogle Scholar
  26. 26.
    Sima AAF, Yagihashi S (1986) Central-peripheral axonopathy in the spontaneously diabetic BB-rat; ultrastructural and morphometric findings. Diabetes Res Clin Prac 1: 289–298CrossRefGoogle Scholar
  27. 27.
    Lampert P, Blumberg JM, Pentschew A (1964) An electron microscopic study of dystrophic axons in the gracile and cuneate nuclei of vitamin E-deficient rats. J Neuropathol Exp Neurol 23: 60–77PubMedCrossRefGoogle Scholar
  28. 28.
    Jellinger K (1973) Neuroaxonal dystrophy: its natural history and related disorders. Prog Neuropathol 2: 129–180Google Scholar
  29. 29.
    Schmidt RE, Plurad SB, Modert CW (1983) Neuroaxonal dystrophy in the autonomic ganglia of aged rats. J Neuropathol Exp Neurol 42: 376–390PubMedCrossRefGoogle Scholar
  30. 30.
    Johnson JE, Mehler WR, Miguel J (1975) A fine structural study of degenerative changes in the dorsal column nuclei of aging mice. Lack of protection by vitamin E. J Gerontol 30: 395–411PubMedCrossRefGoogle Scholar
  31. 31.
    Wisniewski K, Wisniewski HM (1980) Diagnosis of infantile neuroaxonal dystrophy by skin biopsy. Ann Neurol 7: 377–379PubMedCrossRefGoogle Scholar
  32. 32.
    Duncan C, Strub R, McGarry P, Duncan D (1970) Peripheral nerve biopsy as an aid to diagnosis in infantile neuroaxonal dystrophy. Neurol 20: 1024–1032CrossRefGoogle Scholar
  33. 33.
    Berard-Badier M, Gambarelli D, Pinsard N, Hassoun J, Toga M (1971) Infantile neuroaxonal dystrophy or Seitelberger’s disease. II. Peripheral nerve involvement: electron microscopic study in one case. Acta Neuropathol [Suppl] V: 30–39Google Scholar
  34. 34.
    Arsenio-Nunes ML, Gontieres F (1978) Diagnosis of infantile neuroaxonal dystrophy by conjunctival biopsy. J Neurol Neurosurg Psychiatry 41: 511–515PubMedCrossRefGoogle Scholar
  35. 35.
    Martin JJ, Leroy JG, Libert J, van Eygen M, Logghe N (1979) Skin and conjunctival biopsies in infantile neuroaxonal dystrophy. Acta Neuropathol 45: 247–251PubMedCrossRefGoogle Scholar
  36. 36.
    Carlo J, Willis J, McGarry P, Duncan C (1982) Examination of dental pulp to diagnose infantile neuroaxonal dystrophy. Arch Neurol 39: 422–423PubMedCrossRefGoogle Scholar
  37. 37.
    Sima AAF, Yagihashi S (1986) Central-peripheral axonopathy in the spontaneously diabetic BB-rat; ultrastructural and morphometric findings. Diabetes Res Clin Pract 1: 289–298CrossRefGoogle Scholar
  38. 38.
    Cavanagh JB (1979) The “dying back” process. A common denominator in many naturally occurring and toxic neuropathies. Arch Pathol Lab Med 103: 659–664PubMedGoogle Scholar
  39. 39.
    Thomas PK, Schaumburg HH, Spencer PS, Kaeser HE, Pallis CA, Rose C, Wadia NH (1984) Central distal axonopathy syndromes: newly recognized models of naturally occurring human degenerative disease. Ann Neurol 15: 313–315PubMedCrossRefGoogle Scholar
  40. 40.
    Beaudet AL, Thomas GH (1989) Disorders of glycoprotein degradation: mannosidosis, fucosidosis, sialidosis, and aspartylglycosaminuria. In: Scriver CR, Beaudet AL, Sly WS, et al (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill: New York, pp 1603–1621Google Scholar
  41. 41.
    Linden H-U, Klein RA, Egge H, Peter-Katalinic J, Dabrowski J, Schindler D (1989) Isolation and structural characterization of sialic acid-containing glycopeptides of the O-glycosidic type from the urine of two patients with an hereditary deficiency in α-N-acetylgalactosaminidase activity. Biol Chem Hoppe-Seyler 370: 661–672PubMedCrossRefGoogle Scholar
  42. 42.
    Holtzman E (1989) Lysosomes. Plenum Press: New YorkGoogle Scholar
  43. 43.
    Fumagalli G, Engel AG, Lindstrom J (1982) Ultrastructural aspects of acetylcholine receptor turnover at the normal end-plate and in autoimmune myasthenia gravis. J Neuropathol Exp Neurol 41: 567–579PubMedCrossRefGoogle Scholar
  44. 44.
    Goodrum JF, Stone GC, Morell P (1989) Axonal transport and intracellular sorting of glycoconjugates. In: Margolis RU, Margolis RK (eds) Neurobiology of glycoconjugates. Plenum: New York, pp 277–308Google Scholar
  45. 45.
    Harzer K, Cantz M, Sewell AC, Dhareshwar SS, Roggendorf W, Heckl RW, Schofer O, Thumler R, Peiffer J, Scholte W (1986) Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria. Hum Genet 74: 209–214PubMedCrossRefGoogle Scholar
  46. 46.
    Griffin JW, Price DL, Drachman DB, Morris J (1981) Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration. J Cell Biol 88: 205–214PubMedCrossRefGoogle Scholar
  47. 47.
    Harry GJ, Goodrum JF, Toews AD, Morell P (1987) Axonal transport characteristics of gangliosides in sensory axons of rat sciatic nerve. J Neurochem 48: 1529–1536PubMedCrossRefGoogle Scholar
  48. 48.
    Jakobsen J, Sidenius P (1979) Decreased axonal flux of retrogradely transported glycoproteins in early experimental diabetes. J Neurochem 30: 1055–1060CrossRefGoogle Scholar
  49. 49.
    Sidenius P, Jakobsen J (1979) Retrograde axonal transport. A possible role in the development of neuropathy. Diabetologia 20: 110–112CrossRefGoogle Scholar
  50. 50.
    Jakobsen J, Sidenius P (1980) Decreased axonal transport of structural proteins in streptozotocin diabetic rats. J Clin Invest 66: 292–297PubMedCrossRefGoogle Scholar
  51. 51.
    Powers JM, Tummons RC, Moser AB, Huff DS, Kelley RI (1987) Neuronal lipidosis and neuroaxonal dystrophy in cerebro-hepato-renal (Zellweger) syndrome. Acta Neuropathol 73: 333–343PubMedCrossRefGoogle Scholar
  52. 52.
    Kanzaki T, Yokota M, Mizuno Y, Hirabayashi Y (1988) Biochemical studies of novel angiokeratoma corporis diffusum with accumulation of new sialylglycopeptides. Clin Res 36: 660AGoogle Scholar

Copyright information

© Springer-Verlag Wien 1995

Authors and Affiliations

  • D. Wolfe
    • 1
  1. 1.Department of Pathology, Neuropathology DivisionMount Sinai Medical CenterNew YorkUSA

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