Alpha-Mannosidase Deficiency in Persian Cats: A Model of Human Alpha-Mannosidosis

  • Joseph Alroy
  • Kenneth L. Schunk
  • Srinivasa S. Ranghavan
  • Christopher D. Warren
  • Peter F. Daniel
  • Edwin H. Kolodny
Part of the NATO ASI Series book series (NSSA, volume 150)


A family of cats deficient in lysosomal α-mannosidase activity was studied. Analysis of the family pedigree indicated an autosomal recessive mode of inheritance. All affected kittens had frontal bossing, facial coarsening and dysostosis multiplex. They had retarded growth and developed progressive ataxia, tremor, corneal and lenticular opacities, and hepatomegaly. Thin layer chromatography and high pressure liquid chromatography of urine revealed partially degraded N glycoprotein-derived oligosaccharides. Activity of acidic α-mannosidase from plasma and leukocytes of affected kittens was less than 2% of normal, while the enzyme activity of heterozygotes was less than 50%. In blood smears, 90% of circulating lymphocytes were vacuolated. Ultrastructural studies of circulating white blood cells revealed vacuoles containing storage material in various cell types. Affected animals died or were killed at an early age due to the severity of the disease. Most cell types in visceral, neural and skeletal organs were affected. These cells were enlarged, vacuolated and contained fine granular material or appeared empty. The course of this disease in cats and the morphological and biochemical changes, are similar to those seen in the infantile phenotype of human α-mannosidosis.


High Pressure Liquid Chromatography Lysosomal Storage Disease Frontal Boss Autosomal Recessive Mode Lenticular Opacity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beaudet AL. 1983. Disorders of glycoprotein degradation: mannosidosis, fucosidosis, sialidosis and aspartylglucosaminuria. In: Stanbury JB, Wyngaarden JB, Frederickson DAS, Goldstein JL, Brown MS (eds), The Metabolic Basis of Inherited Diseases, 5th ed., Mc-Graw-Hill, New York, pp. 788–802.Google Scholar
  2. 2.
    Kjellman B, Gamstrop I, Brun A, Ockerman P-A, Palmgren B. 1969. Mannosidosis: A clinical and histopathological study. J. Pediat. 75: 366.PubMedCrossRefGoogle Scholar
  3. 3.
    Daniel PF, DeFeudis DF, Lott IT. 1981. Mannosidosis: isolation and comparison of mannose containing oligosaccharides from gingiva and urine. Eur J. Biochem 114: 235.Google Scholar
  4. 4.
    Daniel PF, DeFeudis DF, Lott IT, McLuer RH. 1981. Quantitative microanalysis of oligosaccharides by high performance liquid chromatography. Carbohydr Res 97: 161.Google Scholar
  5. 5.
    Warren CD, Schmit AS, Jeanloz RW. 1983. Chromatographic separation of oligosaccharides from mannosidosis urine. Carbohydr. Res. 116: 171.Google Scholar
  6. 6.
    Arbisser AI, Murphree AL, Garcia CA, Howell RR. 1976. Ocular findings in mannosidosis. Am J Ophthalmol 82: 465.Google Scholar
  7. 7.
    Letson RD, Desnick RJ. 1978. Punctate lenticular opacities in type II mannosidosis. Am J Ophthalmol 82: 218.Google Scholar
  8. 8.
    Burditt LJ, Chotal K, Hirani S, Nuget PG, Winchester BG, Blakemore WF. 1980. Biochemical studies on a case of feline mannosidosis. Biochem J 189: 467.Google Scholar
  9. 9.
    Jolly RD, Slack PM, Winter PJ, Murphy CE. 1980. Mannosidosis: Patterns of storage and urinary excretion of oligosaccharides in the bovine model. AJEBAK 58: 421.Google Scholar
  10. 10.
    Jolly RD, Thompson KG. 1978. The pathology of bovine mannosidosis. Vet Path 15: 141.Google Scholar
  11. 11.
    Jolly RD, Thompson KG, Murphy CE, Manktelon BW, Bruere NA, Winchester BG. 1976. Enzyme replacement therapy: An experiment of nature in chimeric mannosidosis. Pediat Res 10: 219.Google Scholar
  12. 12.
    Walkely SU, Blakemore WF, Purpura DP. 1981. Alterations in neuron morphology in feline mannosidosis: A golgi study. Acta Neuropathol 53: 75.Google Scholar
  13. 13.
    Vandevelde M, Fankhauser R, Bichsei P, Wiesmann U, Herschkowitz N. 1982. Hereditary neurovisceral mannosidosis associated with a-mannosidase deficiency in a family of Persian cats. Acta. Neuropathol. 58: 64.Google Scholar
  14. 14.
    Alroy J, Orgad U, Ucci AA, Pereira MEA. 1984. Identification of glycoprotein storage diseases by lectins: A new diagnostic method. J. Histochem Cytochem 32: 1280.Google Scholar
  15. 15.
    Warren CD, Alroy J, Bugge B, Daniel PF, Raghaven SS, Kolodny EH, Lamar JJ, Jeanloz RW. 1986. Oligosaccharides from placenta: Early diagnosis of feline mannosidosis. FEBS Lett 195: 247.Google Scholar
  16. 16.
    Kolodny, EH, Mumford RA. 1976. Human leukocyte acid hydrolases: Characterization of eleven lysosomal enzymes and study of reaction conditions for their automated analysis. Clin. Chem. Ac. Clin. Chem.Google Scholar
  17. 17.
    Lowry OH, Rosenbrough NJ, Farr AJ, Randall RJ. 1951. Protein measurement with folin phenol reagent. J. Biol. Chem. 193: 265.Google Scholar
  18. 18.
    Dahl DL, Warren CD, Rathke EJS, Jones MZ. 1986. β-mannosidosis: prenatal detection of caprine allantoic fluid oligosaccharides with thin layer, gel permeation and high performance liquid Chromatograph. J Inher Metab Dis 9: 93.Google Scholar
  19. 19.
    Dunphy PJ, Kerr JD, Pennock JF, Whittle KJ, and Feeney J. 1967. The plurality of long chain isoprenoid alcohols (polyprenols) from natural sources. Biochim Biophys Acta 136: 136.Google Scholar
  20. 20.
    Daniel PF, Warren CD, James LF, Jolly RD. 1985. Characterization of oligosaccharides from locoweed-poisoned sheep and comparison with bovine mannosidosis. In: Seawright AA, Hegarty M, James LF, Keeler RJ (eds), Plant Toxicology. Vol. 2. The Queensland Poisonous Plant Committee, Queensland, Australia, pp. 290-300.Google Scholar
  21. 21.
    Robinson JM, Karnovsky MJ. 1983. Ultratructural localization of several phosphatases with cerium. J. Histochem. Cytochem. 31: 1197.Google Scholar
  22. 22.
    Abraham D, Daniel P, Dell A, Oates J, Sidebotham R, Winchester B. 1986. Structural analysis of the major urinary oligosaccharides in feline a-mannosidosis. Biochem J 233: 899.Google Scholar
  23. 23.
    Ockermann P-A. 1967. A generalized storage disorder resembling Hurler’s syndrome. Lancet 2: 239.Google Scholar
  24. 24.
    Hocking JD, Jolly RD, Batt RD. 1972. Deficiency of a-mannosidase in Angus cattle. Biochem J 128: 69.Google Scholar
  25. 25.
    Jezyk PF, Haskins ME, Newman LR. 1986. Alpha-mannosidosis in a Persian cat. JAVMA 189: 1483.Google Scholar
  26. 26.
    Desnick RJ, Sharp HL, Grabowski GA, Brunning RD, Quie PG, Sung JH, Gorlin RJ, Ikonne JU. 1976. Mannosidosis: Clinical, morphologic, immunologic, and biochemical studies. Pediat Res 10: 985.Google Scholar
  27. 27.
    Kistler JP, Lott IT, Kolodny EH, Friedman RB, Nersasian R, Schnur J, Mihm HC, Dvorak AM, Dickersin R. 1977. Mannosidosis: A new clinical presentation, enzyme studies, and carbohydrate analysis. Arch. Neurol. 34: 45.Google Scholar
  28. 28.
    Beaudet AL, Nichols BL. 1976. Residual altered o-mannosidase in human mannosidosis. Biochem Biophys Res Commun 62:292.Google Scholar
  29. 29.
    Burditt LJ, Philips NG, Robinson D, Winchester BG, Van-der-Water NS, Jolly RD. 1978. Characterization of the mutant a-mannosidase in bovine mannosidase. Biochem J 175:1013.Google Scholar
  30. 30.
    Raghavan S, Stuer G, Riviere L, Alroy J, Kolodny EH. 1987. Characterization of alpha-mannosidase in feline mannosidosis. J Inhert Metab Dis 10:(in press).Google Scholar
  31. 31.
    Alroy J, Ucci AA, Warren CD. 1985. Human and canine fucosidosis: A comparative lectin histochemistry study. Acta Neuropathol 67: 265.Google Scholar
  32. 32.
    Yamashita K, Tachibana Y, Mihara K, Okada S, Yabuuchi H, Kobata A. 1980. Urinary oligosaccharides of mannosidosis. J. Biol. Chem. 255: 5126.Google Scholar
  33. 33.
    Mason AJ, Pitts SL, Nikolics K, Szonyi E, Wilcox JN, Seeburg PH, Stewart TA. 1986. The hypogonadal mouse: Reproductive functions restored by gene therapy. Sci 236: 1372.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Joseph Alroy
    • 1
    • 2
    • 3
  • Kenneth L. Schunk
    • 1
    • 2
    • 3
  • Srinivasa S. Ranghavan
    • 1
    • 2
    • 3
  • Christopher D. Warren
    • 1
    • 2
    • 3
  • Peter F. Daniel
    • 1
    • 2
    • 3
  • Edwin H. Kolodny
    • 1
    • 2
    • 3
  1. 1.Massachusetts General HospitalBostonUSA
  2. 2.Tufts UnivesityBostonUSA
  3. 3.Grafton E.K. Shriver Center WalthamUSA

Personalised recommendations