Advertisement

Zeitschrift für Kinderheilkunde

, Volume 114, Issue 4, pp 259–292 | Cite as

I-Cell disease, mucolipidosis II

Pathological, histochemical, ultrastructural and biochemical observations in four cases
  • Enid F. Gilbert
  • Glyn Dawson
  • Gabriele M. Zu Rhein
  • John M. Opitz
  • Jürgen W. Spranger
Article

Abstract

Pathological, histochemical, ultrastructural and biochemical studies on 4 cases of I-cell disease are reported. These studies support a lysosomal defect with deficiency of many acid hydrolases and storage of both glycolipids and mucopolysaccharides within lysosomes. The clinical, pathological and biochemical spectra of I-cell disease in these 4 cases suggest three distinct nosologic entities: a prototype, a malignant infantile form and a more benign juvenile type. Consanguinity was present in one of the cases. An autosomal recessive mode of inheritance seems most likely.

Key words

Storage disease Mucopolysaccharidosis Mucolipidosis Lysosomes Glycolipids Sphingolipids Mucopolysaccharides Lysosomal hydrolases Neurodegenerative disorders 

Zusammenfassung

Darstellung der klinischen, pathologischen, elektronenoptischen, histochemischen und biochemischen Untersuchungsergebnisse von 4 Patienten mit “I-cell disease” (Mucolipidose II). Charakteristisch sind das Hurler-ähnliche klinische Erscheinungsbild bei normaler Mucopolysaccharidurie und grobkörnige Einschlüsse in gezüchteten Fibroblasten. Pathohistologisch beeindrucken u. a. ausgeprägte Speicherphänomene in Histiocyten. Bei einem Patienten fanden sich in Lunge und Leber eigenartige Lipoidgranulome. Elektronenoptisch zeigten sich intraplasmatische Membransäcke mit polymorphen, teilweise lamellären Einschlüssen. Histochemisch handelte es sich bei den Speichersubstanzen um Glykosphingolipide und andere kohlenhydrathaltige Substanzen. Biochemisch wurden in der Leber vermehrte Mengen verschiedener Glykosphingolipide nachgewiesen, insbesondere Trihexosid-Ceramid und GM3-Gangliosid. Ein Patient speicherte Sulfatid in Leber und grauer Hirnsubstanz. Der “I-cell disease” liegen multiple Defekte lysosomaler Enzyme vorwiegend in Zellen mesenchymaler Herkunft zugrunde. Sie führen zur intracellulären Anhäufung eines bunten Gemischs von Lipiden und kohlenhydrathaltigen Substanzen, u. a. Mucopolysacchariden. Wahrscheinlich verbergen sich unter dem Begriff der “I-cell disease” (Mucolipidose II) mehrere Krankheitsbilder.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Leroy, J. G., De Mars, R. I., Opitz, J. M.: “I-cell” disease, In: First Conference on the Clinical Delineation of Birth Defects; Birth Defects Original Article Series, The National Foundation—March of Dimes, New York, N.Y., Vol. V, part 4, 174 (1969).Google Scholar
  2. 2.
    De Mars, R. I., Leroy, J. G.: The remarkable cells cultured from a human with Hurler's syndrome: An approach to visual selection for in vitro genetic studies. In: In Vitro (Tissue Culture Association)2, 107 (1967).Google Scholar
  3. 3.
    Hanai, J., Leroy, J., O'Brien, J. S.: Ultrastructure of cultured fibroblasts in I-cell disease. Amer. J. Dis. Child.122, 34 (1971).Google Scholar
  4. 4.
    Kenyon, K. R., Sensenbrenner, J. A.: Mucolipidosis II (I-cell disease): Ultrastructural observations of conjunctiva and skin. Invest. Ophthal.10, 555 (1971).Google Scholar
  5. 5.
    Tondeur, M., Vamos-Hurwitz, E., Mockel-Pohl, S., Dereume, F. P., Cremer, N., Loeb, H.: Clinical, biochemical and ultrastructural studies in a case of chondrodystrophy presenting the I-cell phenotype in tissue culture. J. Pediat.79, 366 (1971).Google Scholar
  6. 6.
    Spranger, J. W., Wiedemann, H. R.: The genetic mucolipidoses. Diagnosis and differential diagnosis. Humangenetik9, 113 (1970).Google Scholar
  7. 7.
    Faure, C., Kaufman, H. J., Kozlowski, K., Langer, C. O., Lefebre, J., Maroteaux, P., Sauvegrain, J., Silverman, F. N., Spranger, J.: A nomenclature for constitutional intrinsic disease of bone. Ann. Radiol.13, 455 (1970).Google Scholar
  8. 8.
    Leroy, J. G., Spranger, J., Feingold, M., Opitz, J. M., Crocker, A. C.: I-cell disease; a clinical picture. J. Pediat.79, 360 (1971).Google Scholar
  9. 9.
    Rhodin, J.: Correlation of ultrastructural organization and function in normal and experimentally changed proximal convoluted tubule cells of the mouse kidney. Dissertation (Karolinska Institutet), Stockholm 1954.Google Scholar
  10. 10.
    Glauert, A. M., Glauert, R. H.: Araldite as an embedding medium for electron microscopy. J. biophys. biochem. Cytol.4, 191–194 (1958).Google Scholar
  11. 11.
    Seifert, K.: Zur Orientierung inhomogener Gewebeeinbettungen für die Ultramikrotomie. Mikroskopie17, 231 (1962).Google Scholar
  12. 12.
    Vance, D. E., Sweeley, C. C.: Quantitative determination of the neutral glycosyl-ceramides in human blood. J. Lipid Res.8, 621 (1967).Google Scholar
  13. 13.
    Dawson, G.: Glycosphingolipid levels in an unusual neurovisceral storage disease characterized by lactosylceramide galactosyl hydrolase deficiency; Lactosyl-ceramidosis. J. Lipid Res.13, 207 (1972).Google Scholar
  14. 14.
    Clamp, J. R., Dawson, G., Hough, L.: The simultaneous estimation of 6-deoxy-L-galactose (L-fucose), D-mannose, D-galactose, 2-acetamido-2 deoxy-D-glucose (N-acetyl-D-glucosamine) andN-acetylneuraminic acid (sialic acid) in glycopeptides and glycoproteins. Biochim. biophys. Acta (Amst.)148, 342 (1967).Google Scholar
  15. 15.
    Moser, H. W.: Sulfatide lipidosis. In: Metachromatic leukodystrophy in metabolic basis of inherited disease, pp. 688, Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S. (Eds.). New York: McGraw-Hill 1972.Google Scholar
  16. 16.
    Landing, B. H., Silverman, F. N., Craig, J. M., Jacoby, M. D., Lahey, M. E., Chadwick, D. L.: Familial neurovisceral lipidosis. Amer. J. Dis. Child.108, 503 (1964).Google Scholar
  17. 17.
    O'Brien, J.: Generalized gangliosidosis. J. Pediat.75, 167 (1969).Google Scholar
  18. 18.
    Kenyon, K. R., Wyllie, R. G., Sensenbrenner, J. A.: Hepatic ultrastructure and histochemistry in mucolipidosis II (I-cell disease). Amer. J. Path. To be published.Google Scholar
  19. 19.
    Callahan, W. P., Lorincz, A. E.: Hepatic ultrastructure in the Hurler syndrome. Amer. J. Path.48, 277 (1966).Google Scholar
  20. 20.
    Gonatas, N. K., Gonatas, J.: Ultrastructural and biochemical observation on a case of systemic late infantile lipidosis and its relationship to Tay-Sachs disease and gargoylism. J. Neuropath. exp. Neurol.24, 318 (1965).Google Scholar
  21. 21.
    Loeb, H., Tondeur, M., Toppet, M., Cremer, N.: Clinical biochemical and ultrastructural studies of an atypical form of mucopolysaccharidosis. Acta paediat. scand.58, 220 (1969).Google Scholar
  22. 22.
    Haust, M. D., Orizaga, M., Bryans, A. M., Frank, H. F.: The fine structure of liver in children with Hurler's syndrome. Exp. molec. Path.10, 141 (1969).Google Scholar
  23. 23.
    Terry, R. D., Korey, S. R.: Membranous cytoplasmic granules in infantile amaurotic idiocy. Nature (Lond.)188, 1000 (1960).Google Scholar
  24. 24.
    Terry, R. D., Weiss, M.: Studies on Tay-Sachs disease: II. Ultrastructure of the cerebrum. J. Neuropath. exp. Neurol.22, 18 (1963).Google Scholar
  25. 25.
    Adachi, M., Torii, J., Schneck, L., Volk, B. W.: The fine structure of fetal Tay-Sachs disease. Arch. Path.91, 48 (1971).Google Scholar
  26. 26.
    Suzuki, Y., Jacob, J. C., Suzuki, K., Kutty, K. M., Suzuki, K.: GM2-gangliosidosis with total hexosaminidase deficiency. Neurology (Minneap.)20, 338 (1971).Google Scholar
  27. 27.
    Freitag, F. S., Blumcke, S., Spranger, J.: Hepatic ultrastructure in mucolipidosis I (lipomucopolysaccharidosis). Virchows Arch. Abt. B Zellpath.7, 189 (1971).Google Scholar
  28. 28.
    Freitag, F., Kuchemann, D., Blumcke, S., Spranger, J.: Hepatic ultrastructure in fucosidosis. Virchows Arch. Abt. B. Zellpath.7, 99 (1971).Google Scholar
  29. 29.
    Hoof, F. van, Hers, H. G.: L'ultrastructure des cellules hepatiques dans la maladie de Hurler (gargoylisme). C. R. Acad. Sci. (Paris)259, 1281 (1964).Google Scholar
  30. 30.
    Durand, P., Borrone, C., Della cella, G.: A new mucopolysaccharide lipid storage disease? Lancet1966 II, 1313.Google Scholar
  31. 31.
    Taketomi, T., Yamakawa, T.: Glycolipids of the brain in gargoylism. Jap. J. exp. Med.37, 11 (1967).Google Scholar
  32. 32.
    Matalon, R., Dorfman, A.: Hurler's syndrome, an α-L-iduronidase deficiency. Biochem. biophys. Res. Commun.47, 959 (1972).Google Scholar
  33. 33.
    Leroy, J. G., De Mars, R. I.: Mutant enzymatic and cytological phenotypes in cultured human fibroblasts. Science157, 804 (1967).Google Scholar
  34. 34.
    Matalon, R., Cifonelli, J. A., Zellweger, H., Dorfman, A.: Lipid abnormalities in a variant of the Hurler syndrome. Proc. nat. Acad. Sci. (Wash.)59, 1097 (1968).Google Scholar
  35. 35.
    Dawson, G., Matalon, R., Dorfman, A.: Glycosphingolipids in cultured human skin fibroblasts from patients with inborn errors of glycosphingolipid and mucopolysaccharide metabolism. J. biol. Chem.247, 5951 (1972).Google Scholar
  36. 36.
    Neufeld, E. F., Cantz, M.: Personal communication 1972.Google Scholar
  37. 37.
    Leroy, J. G., Wan Ho, M., MacBrinn, M. C., Zielke, K., Jacob, J., O'Brien, J. S.: I-cell disease: biochemical studies. Pediat. Res.6, 752 (1972).Google Scholar
  38. 38.
    Wiesmann, U. N., Lightbody, J., Vassella, F., Herschkowitz, N.: Multiple lysosomal enzyme deficiency due to enzyme leakage? New Engl. J. Med.284, 109 (1971).Google Scholar
  39. 39.
    Wiesmann, U., Vassella, F., Herschkowitz, N.: “I-cell” disease: Leakage of lysosomal enzymes into extracellular fluids. New Engl. J. Med.285, 1090 (1971).Google Scholar
  40. 40.
    Hickman, S., Neufeld, E. F.: A hypothesis for I-cell disease: defective hydrolases that do not enter lysosomes. Biochem. biophys. Res. Commun.49, 992 (1972).Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • Enid F. Gilbert
    • 1
  • Glyn Dawson
    • 2
  • Gabriele M. Zu Rhein
    • 3
  • John M. Opitz
    • 3
  • Jürgen W. Spranger
    • 4
  1. 1.Center for Health Science and Medical SchoolUniversity of WisconsinMadison
  2. 2.Departments of Pediatrics and BiochemistryUniversity of ChicagoChicago
  3. 3.University of Wisconsin Center for Health Sciences and Medical SchoolMadison
  4. 4.Department of PediatricsUniversity Children's HospitalKiel

Personalised recommendations