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.
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References
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: 349–357
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: 1735–1740
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 1751–1798
Wolfe DE, Schindler D, Desnick RJ, Perl D (1989) Infantile neuroaxonal dystrophy (INAD) associated with a lysosomal enzyme deficiency. J Neuropathol Exp Neurol 48: 349
Peters A, Palay S, Webster HdeF (1991) The fine structure of the nervous system, 3rd edn. Saunders: Philadelphia
Kamoshita S, Neustein HB, Landing BH (1968) Infantile neuroaxonal dystrophy with neonatal onset. Neuropathologic and electron microscopic observations. J Neuropathol Exp Neurol 27: 300–323
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: 261–267
Goebel HH, Kohlschutter A, Schulte FJ (1980) Rectal biopsy findings in infantile neuroaxonal dystrophy. Neuropediatrics 11: 388–392
Schmidt RE, Plurad SB (1986) Ultrastructural and biochemical characterization of autonomic neuropathy in rats with chronic streptozotocin diabetes. J Neuropathol Exp Neurol 45: 525–544
Yagihashi S, Sima AAF (1986) Diabetic autonomic neuropathy in the BB rat. Ultra-structural and morphometric changes in parasympathetic nerves. Diabetes 35: 733–743
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: 77–92
Yagihashi S, Sima AAF (1988) Diabetic autonomic neuropathy in the BB rat. Frontiers in diabetes research: lessons from animal diabetes II: 477–481
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: 545–565
Spencer PS, Schaumburg HH (1976) Central-peripheral distal axonopathy — the pathology of dying-back polyneuropathies. Prog Neuropathol 3: 253–295
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: 571–597
Bouldin TW, Cavanagh JB (1979) Organophosphorus neuropathy. II. A fine-structural study of the early stages of axonal degeneration. Am J Pathol 94: 253–270
Blakemore WF, Cavanagh JB (1969) “Neuroaxonal dystrophy” occurring in an experimental “dying-back” process in the rat. Brain 92: 789–804
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: 260–284
Sahenk Z, Mendell JR (1979) Ultrastructural study of zinc pyridinethione-induced peripheral neuropathy. J Neuropathol Exp Neurol 38: 532–550
Martin JJ, Martin L (1972) Infantile neuroaxonal dystrophy: ultrastructural study of the peripheral nerves and of the motor end plates. Eur Neurol 8: 239–250
Shimono M, Ohta M, Asada M, Kuroiwa J (1976) Infantile neuroaxonal dystrophy. Ultrastructural study of peripheral nerve. Acta Neuropathol 36: 71–79
Williamson K, Sima AAF, Curry B, Ludwin SK (1982) Neuroaxonal dystrophy in young adults: a clinicopathological study of two unrelated cases. Ann Neurol 11: 335–343
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: 327–350
Aicardi J, Castelein P (1979) Infantile neuroaxonal dystrophy. Brain 102: 727–748
Yagihashi S, Sima AAF (1985) Diabetic autonomic neuropathy in the BB rat. Ultra-structural and morphometric changes in sympathetic nerves. Diabetes 34: 558–564
Sima AAF, Yagihashi S (1986) Central-peripheral axonopathy in the spontaneously diabetic BB-rat; ultrastructural and morphometric findings. Diabetes Res Clin Prac 1: 289–298
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: 60–77
Jellinger K (1973) Neuroaxonal dystrophy: its natural history and related disorders. Prog Neuropathol 2: 129–180
Schmidt RE, Plurad SB, Modert CW (1983) Neuroaxonal dystrophy in the autonomic ganglia of aged rats. J Neuropathol Exp Neurol 42: 376–390
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: 395–411
Wisniewski K, Wisniewski HM (1980) Diagnosis of infantile neuroaxonal dystrophy by skin biopsy. Ann Neurol 7: 377–379
Duncan C, Strub R, McGarry P, Duncan D (1970) Peripheral nerve biopsy as an aid to diagnosis in infantile neuroaxonal dystrophy. Neurol 20: 1024–1032
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: 30–39
Arsenio-Nunes ML, Gontieres F (1978) Diagnosis of infantile neuroaxonal dystrophy by conjunctival biopsy. J Neurol Neurosurg Psychiatry 41: 511–515
Martin JJ, Leroy JG, Libert J, van Eygen M, Logghe N (1979) Skin and conjunctival biopsies in infantile neuroaxonal dystrophy. Acta Neuropathol 45: 247–251
Carlo J, Willis J, McGarry P, Duncan C (1982) Examination of dental pulp to diagnose infantile neuroaxonal dystrophy. Arch Neurol 39: 422–423
Sima AAF, Yagihashi S (1986) Central-peripheral axonopathy in the spontaneously diabetic BB-rat; ultrastructural and morphometric findings. Diabetes Res Clin Pract 1: 289–298
Cavanagh JB (1979) The “dying back” process. A common denominator in many naturally occurring and toxic neuropathies. Arch Pathol Lab Med 103: 659–664
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: 313–315
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 1603–1621
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: 661–672
Holtzman E (1989) Lysosomes. Plenum Press: New York
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: 567–579
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 277–308
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: 209–214
Griffin JW, Price DL, Drachman DB, Morris J (1981) Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration. J Cell Biol 88: 205–214
Harry GJ, Goodrum JF, Toews AD, Morell P (1987) Axonal transport characteristics of gangliosides in sensory axons of rat sciatic nerve. J Neurochem 48: 1529–1536
Jakobsen J, Sidenius P (1979) Decreased axonal flux of retrogradely transported glycoproteins in early experimental diabetes. J Neurochem 30: 1055–1060
Sidenius P, Jakobsen J (1979) Retrograde axonal transport. A possible role in the development of neuropathy. Diabetologia 20: 110–112
Jakobsen J, Sidenius P (1980) Decreased axonal transport of structural proteins in streptozotocin diabetic rats. J Clin Invest 66: 292–297
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: 333–343
Kanzaki T, Yokota M, Mizuno Y, Hirabayashi Y (1988) Biochemical studies of novel angiokeratoma corporis diffusum with accumulation of new sialylglycopeptides. Clin Res 36: 660A
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Wolfe, D. (1995). Infantile neuroaxonal dystrophy associated with α-N-acetylgalactosaminidase deficiency: on relating axonal spheroids to a lysosomal enzyme deficiency. In: Asbury, A.K., Budka, H., Sluga, E. (eds) Sensory Neuropathies. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6595-9_20
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DOI: https://doi.org/10.1007/978-3-7091-6595-9_20
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