Diseases of Carbohydrate Metabolism

  • Reinhard L. Friede


Two important principles which now pervade the entire field of heritable metabolic diseases originated in research on the etiology of glycogen storage diseases. The first principle, now generally applied to inherited metabolic disorders, derives from the proposal by Cori (1957) to classify types of glycogen storage diseases according to the deficient enzyme rather than in terms of organ involvement. The second principle grew out of chemical and electron microscopic studies on glycogen storage disease type II (acid maltase deficiency). Electron microscopic studies in this disease showed glycogen distributed in two forms, freely dispersed throughout the cytoplasm and enclosed in membranebounded vacuoles which were identified as lysosomes (Baudhuin et al., 1964). As acid maltase is a lysosomal enzyme, it was concluded that an inability of the lysosomes to degrade glycogen after its inclusion into the organelle was the key feature of the disease process. The concept of lysosomal disability caused by deficiencies of specific lysosomal enzymes has proven extremely useful for the understanding of many other storage diseases.


Glycogen Storage Disease Dermatan Sulfate Glycogen Storage Disease Type Hunter Syndrome Hurler Syndrome 
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  1. Alder, A.: Über konstitutionell bedingte Granulationsveränderungen der Leucocyten. Dtsch. Arch. klin. Med. 183: 372–378, 1939.Google Scholar
  2. Aleu, F. P., Terry, R. D., Zellweger, H.: Electron microscopy of two cerebral biopsies in gargoylism. J. Neuropath. exp. Neurol. 24: 304–317, 1965.PubMedCrossRefGoogle Scholar
  3. Arstila, A. U., Palo, J., Haltia, M., Riekkinen, P., Autio, S.: Aspartyl-glucosaminuria I: Fine structural studies on liver, kidney and brain. Acta neuropath. (Berl.) 20: 207–216, 1972.CrossRefGoogle Scholar
  4. Bach, G., Eisenberg, F., Jr., Cantz, M., Neufeld, E. F.: The defect in the Hunter syndrome: Deficiency of sulfoiduronate sulfatase. Proc. nat. Acad. Sci. (U.S.A.) 70: 2134–2138, 1973.CrossRefGoogle Scholar
  5. Baudhuin, P., Hers, H. G., Loeb, H.: An electron microscopic and biochemical study of type II glycogenosis. Lab. Invest. 13: 1139–1152, 1964.PubMedGoogle Scholar
  6. Belcher, R. W.: Ultrastructure and cytochemistry of lymphocytes in the genetic mucopolysaccharidoses. Arch. Path. 93: 1–7, 1972.PubMedGoogle Scholar
  7. Bishton, R. L., Norman, R. M., Tingey, A.: The pathology and chemistry of a case of gargoylism. J. clin. Path. 9: 305–315, 1956.PubMedCrossRefGoogle Scholar
  8. Blaw, M. E., Langer, L. O.: Spinal cord compression in Morquio-Brailsford’s disease. J. Pediat. 74: 593–600, 1969.PubMedCrossRefGoogle Scholar
  9. Brante, G.: Gargoylism—a mucopolysaccharidosis. Scand. J. clin. Lab. Invest. 4: 43–46, 1952.PubMedCrossRefGoogle Scholar
  10. Cori, G. T.: Biochemical aspect of glycogen deposition disease. Mod. Probl. Paediat. 3: 344–358, 1957.Google Scholar
  11. Crome, L.: A case of galactosemia with the pathological and neuropathological findings. Arch. Dis. Child. 37: 415–521, 1962.PubMedCrossRefGoogle Scholar
  12. Crome, L.: Cumings, J. N., Duckett, S.: Neuropathologic and neurochemical aspects of generalized glycogen storage disease. J. Neurol. Neurosurg. Psychiat. 26: 422–430, 1963.PubMedCrossRefGoogle Scholar
  13. Dawson, I. M. P.: The histology and histochemistry of gargoylism. J. Path. Bact. 67: 587–604, 1954.PubMedCrossRefGoogle Scholar
  14. Dekaban, A. S., Constantopoulos, G.: Mucopolysaccharidoses. Relation of elevated cerebral spinal fluid to mental retardation. Arch. Neurol. (Chic.) 28: 385–388, 1973.CrossRefGoogle Scholar
  15. Dekaban, A. S., Patton, V.: Hurler’s and Sanfilippo’s variants of mucopolysaccharidosis. Arch. Path. (Chic.) 91: 434–443, 1971.Google Scholar
  16. Diezel, P. B.: Histochemische Untersuchungen an primären Lipoidosen: Amaurotische Idiotie, Gargoylismus, Niemann-Picksche Krankheit, Gauchersche Krankheit, mit besonderer Berücksichtigung des Zentralnervensystems. Virchows Arch. 326: 89–118, 1954.PubMedCrossRefGoogle Scholar
  17. Durand, P., Barrone, C., Della Cella, G.: Fucosidosis. J. Pediat. 75: 665–674, 1969.PubMedCrossRefGoogle Scholar
  18. Gambetti, P., Di Mauro, S., Baker, L.: Nervous system in Pompe’s disease. Ultrastructure and biochemistry. J. Neuropath. exp. Neurol. 30: 412–430, 1971.PubMedCrossRefGoogle Scholar
  19. Gerich, J. E.: Hunter’s syndrome. Beta-galactosidase deficiency in skin. New Engl. J. Med. 280: 799–802, 1969.PubMedCrossRefGoogle Scholar
  20. Gilles, F. H., Deuel, R. K.: Neuronal cytoplasmic globules in the brain in Morquio’s syndrome. Arch. Neurol. (Chic.) 25: 393–403, 1971.CrossRefGoogle Scholar
  21. Gonatas, N. K., Gonatas, J.: Ultrastructural and biochemical observations on a case of systemic late infantile lipidosis and its relationship to Tay-Sachs disease and gargoylism. J. Neuropath. exp. Neurol. 24: 318–340, 1965.PubMedCrossRefGoogle Scholar
  22. Green, M. A.: Gargoylism (lipochondrodystrophy). J. Neuropath. exp. Neurol. 7: 399–417, 1948.PubMedCrossRefGoogle Scholar
  23. Haberland, C., Perou, M., Brunngraber, E. G., Hof, H.: The neuropathology of galactosemia. A histopathological and biochemical study. J. Neuropath. exp. Neurol. 30: 431–447, 1971.PubMedCrossRefGoogle Scholar
  24. Hers, H. G.: α-glucosidase deficiency in generalized glycogen storage disease (Pompe’s disease). Biochem. J. 86: 11–16, 1963.PubMedGoogle Scholar
  25. Hers, H. G., de Barsy, T.: Type II glycogenosis (acid maltase deficiency). In: Lysosomes and Storage Diseases (Hers, H. G., van Hoof, F., eds.), pp. 197–216. New York: Academic Press 1973.Google Scholar
  26. Howell, R. R.: The glycogen storage diseases. In: The Metabolic Basis of Inherited Diseases (Stanbury, J. B., Wyngaarden, J. B., Fredricksen, D. S., eds.), Chapter VII. New York: McGraw-Hill 1972.Google Scholar
  27. Hug, G., Garancis, J. C., Schubert, W. K., Kaplan, S.: Glycogen storage disease Types II, III, VIII, and IX. Amer. J. Dis. Child. 11: 457–474, 1966.Google Scholar
  28. Hug, G., Schubert, W. K.: Glycogenosis associated with degenerative disease of the brain: biochemical and electron microscopic findings. Clin. Res. 14: 441–441, 1966.Google Scholar
  29. Hug, G., Schubert, W. K., Chuck, G., Garancis, J. C.: Liver phosphorylase. Deactivation in a child with progressive brain disease, increased hepatic glycogen and increased urinary catecholamines. Amer. J. Med. 42: 139–145, 1967.PubMedCrossRefGoogle Scholar
  30. Hunter, C.: Rare disease in two brothers. Proc. Roy. Soc. Med. 10: 104–116, 1917.PubMedGoogle Scholar
  31. Hurler, G.: Über einen Typ multipler Abartungen, vorwiegend am Skelettsystem. Z. Kinderheilk. 24: 220–234, 1919.CrossRefGoogle Scholar
  32. Huttenlocher, P. R., Hillman, R. E., Hsia, Y. E.: Pseudotumor cerebri in galactosemia. J. Pediat. 76: 902–905, 1970.PubMedCrossRefGoogle Scholar
  33. Jenner, F. A., Pollitt, R. J.: Large quantities of 2-acetamido-1(β1-L-aspartamido)1,2-dideoxyglucose in the urine of mentally retarded siblings. Biochem. J. 103: 48–48, 1967.Google Scholar
  34. Jervis, G. A.: Gargoylism (lipochondrodystrophy). Arch. Neurol. Psychiat. (Chic.) 63: 681–712, 1950.Google Scholar
  35. Kalckar, H. M., Anderson, E. P., Isselbacher, K. J.: Galactosemia, a congenital defect in a nucleotide transferase. Biochem. Biophys. Acta 20: 262–268, 1956.PubMedCrossRefGoogle Scholar
  36. Kjellman, B., Gamstrop, I., Brun, A., Ockerman, P. A., Palmgren, B.: Mannosidosis: a clinical and histopathologic study. J. Pediat. 75: 366–373, 1969.PubMedCrossRefGoogle Scholar
  37. Kresse, H.: Mucopolysaccharidosis III A (Sanfilippo A disease): Deficiency of a heparin sulfamidase in skin fibroblasts and leukocytes. Biochem. biophys. Res. Commun. 54: 1111–1118, 1973.PubMedCrossRefGoogle Scholar
  38. Kresse, H., Neufeld, E. F.: The Sanfilippo A corrective factor. J. Biol. Chem. 247: 2164–2170, 1972.PubMedGoogle Scholar
  39. Ledeen, R., Salsman, K., Gonatas, J., Tachavy, A.: Structure comparison of the major monosialogangliosides from brains of normal human gargoylism and late infantile systemic lipidosis. J. Neuropath. exp. Neurol. 24: 341–351, 1965.PubMedCrossRefGoogle Scholar
  40. Loeb, H., Tondeur, M., Résibois, A., Jonniaux, G., Van Hoof, F.: in: Proceedings of the Sixth Symposium of the Society of the Study of Inborn Errors of Metabolism (Allan, J. D., et al., eds.), pp. 94–95. Edinburgh: Livingstone 1969.Google Scholar
  41. McAdams, A. J., Hug, G., Bove, K. E.: Glycogen storage disease. Types I to X: Criteria for morphologic diagnosis. Human Path. 5: 463–488, 1974.CrossRefGoogle Scholar
  42. McKusick, V. A.: Heritable Disorders of Connective Tissue, Fourth edition. St. Louis: Mosby 1972.Google Scholar
  43. McKusick, V. A., Kaplan, D., Wise, D., et al.: The genetic mucopolysaccharidoses. Medicine 44: 445–483, 1965.PubMedCrossRefGoogle Scholar
  44. Magee, K. R.: Leptomeningeal change associated with lipochondrodystrophy (gargoylism). Arch. Neurol. Psychiat. (Chic.) 63: 282–297, 1950.Google Scholar
  45. Mancall, E. L., Aponte, G. E., Berry, R. G.: Pompe’s disease (diffuse glycogenosis) with neuronal storage. J. Neuropath. exp. Neurol. 24: 85–96, 1965.PubMedCrossRefGoogle Scholar
  46. Martin, J. J., de Barsy, Th., Van Hoof, F., Palladini, G.: Pompe’s disease: An inborn lysosomal disorder with storage of glycogen. A study of brain and striated muscle. Acta Neuropath. (Berl.) 23: 229–244, 1973.CrossRefGoogle Scholar
  47. Matalon, R., Cifonelli, J. A., Dorfman, A.: L-iduronidase in cultured human fibroblasts and liver. Biochem. biophys. Res. Commun. 42: 340–345, 1971.PubMedCrossRefGoogle Scholar
  48. Matalon, R., Dorfman, A.: Hurler’s syndrome, an α-L-iduronidase deficiency. Biochem. biophys. Res. Commun. 47: 959–964, 1972.PubMedCrossRefGoogle Scholar
  49. Naidoo, P.: Gargoylism (Hurler’s disease): A neuropathological report. J. ment. Sci. 99: 74–83, 1953.PubMedGoogle Scholar
  50. Neufeld, E. F., Cantz, M.: The mucopolysaccharidoses studies in cell culture. In: Lysosomes and Storage Diseases (Hers, H. G., Van Hoof, F., eds.), pp. 262–275. New York: Academic Press 1973.Google Scholar
  51. Norman, R. M., Urich, H., France, N. E.: Perivascular cavitation of the basal ganglia in gargoylism. J. ment. Sci. 105: 1070–1077, 1959.PubMedGoogle Scholar
  52. O’Brien, J. S.: Sanfilippo syndrome: Profound deficiency of alpha-acetyl-glucosaminidase activity in organs and skin fibroblasts from type B patients. Proc. nat. Acad. Sci. 69: 1720–1722, 1972.PubMedCrossRefGoogle Scholar
  53. Ockerman, P. A.: Mannosidosis. In: Lysosomes and Storage Diseases (Hers, G. H., Van Hoof, F., eds.), Chapter 11. New York: Academic Press 1973.Google Scholar
  54. Ockerman, P. A., Köhlin, P.: Glycosidases in skin and plasma in Hunter syndrome. Acta paed. Scand. 57: 281–284, 1968.CrossRefGoogle Scholar
  55. Palo, J., Mattsson, K.: Eleven new cases of aspartylglucosaminuria. J. ment. Defic. Res. 14: 168–173, 1970.PubMedGoogle Scholar
  56. Reilly, W. A.: The granules in the leucocytes in gargoylism. Amer. J. Dis. Child. 62: 489–491, 1941.Google Scholar
  57. Résibois-Grégoire, A., Dourov, N.: Electron microscopic study of a case of cerebral glycogenosis. Acta neuropath. (Berl.) 6: 70–79, 1966.CrossRefGoogle Scholar
  58. Roukema, P. A., Oderkerk, C. H., van den Berg, G.: Gargoylism (mucopolysaccharidosis type II). Accumulation of glycosaminoglycans, gangliosides and glycoproteins and activity of some related glycolytic enzymes in liver, spleen and brain. Clin. Chim. Acta 44: 277–286, 1973.PubMedCrossRefGoogle Scholar
  59. Sandström, B., Westman, J., Öckerman, P. A.: Glycogenosis of the central nervous system in the cat. Acta neuropath. (Berl.) 14: 194–200, 1969.CrossRefGoogle Scholar
  60. Schnabl, R.: Über die Speicherung mucopolysaccharidartiger Substanzen im Gehirn bei generalisierter Glykogenose (Type II). Acta neuropath. (Berl.) 4: 646–658, 1965.CrossRefGoogle Scholar
  61. Schochet, S. S., Jr., McCormick, W. F., Halmi, N. S.: Pituitary gland in patients with Hurler syndrome. Arch. Path. (Chic.) 97: 96–99, 1974.Google Scholar
  62. Schwarz, V., Golberg, L., Komrower, G. M., Holzel, A.: Some disturbances of erythrocyte metabolism in galactosemia. Biochem. J. 62: 34–40, 1956.PubMedGoogle Scholar
  63. Seitelberger, F.: The position of gargoylism amongst the sphingolipidoses on the basis of the histochemistry of cellular storage substances. In: Cerebral lipidoses (Cumings, J. N., ed.), pp. 77–91. Springfield, Ill.: Ch. C Thomas 1957.Google Scholar
  64. Toussaint, D., Danis, P.: Ocular histopathology in generalized glycogenosis (Pompe’s disease). Arch. Ophthal. (Chic.) 73: 342–349, 1965.Google Scholar
  65. Tuthill, C. R.: Juvenile amaurotic idiocy. Arch. Neurol. Psychiat. (Chic.) 32: 198–209, 1934.Google Scholar
  66. Uchimura, Y., Toshima, Y., Sekeiya, T.: Zur elektronenmikroskopischen Pathomorphologie der Hirnrinde bei Gargoylismus. Acta neuropath. (Berl.) 4: 476–490, 1965.CrossRefGoogle Scholar
  67. Van Hoof, F.: Fucosidosis. In: Lysosomes and Storage Diseases (Hers, H. G., Van Hoof, F., eds.), Chapter 10. New York: Academic Press 1973.Google Scholar
  68. Wallace, B. J., Kaplan, D., Adachi, M., Schneck, L., Volk, B. W.: Mucopolysaccharidosis type III. Morphologic and biochemical studies of two siblings with Sanfilippo syndrome. Arch. Path. (Chic.) 82: 462–473, 1966.Google Scholar
  69. Wallace, B. J., Schneck, L., Kaplan, H., Volk, B.: Fine structure of the cerebellum of children with lipidoses. Arch. Path. (Chic.) 80: 466–486, 1965.Google Scholar
  70. Wolfe, H. J., Blennerhasset, J. B., Young, G. F., Cohen, R. B.: Hurler’s syndrome. A histochemical study. New techniques for localization of very water-soluble acid mucopolysaccharides. Amer. J. Path. 45: 1007–1027, 1964.PubMedGoogle Scholar
  71. Wolfe, H. J., Cohen, R. B.: Nonglycogen polysaccharide storage in glycogenosis type 2. Arch. Path. (Chic.) 86: 579–584, 1968.Google Scholar

Copyright information

© Springer-Verlag Wien 1975

Authors and Affiliations

  • Reinhard L. Friede
    • 1
    • 2
  1. 1.Case Western Reserve UniversityClevelandUSA
  2. 2.University of ZurichSwitzerland

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