Neurochemical Pathology

, Volume 2, Issue 3, pp 189–218 | Cite as

Biochemical aspects of globoid and metachromatic leukodystrophies

  • Akhlaq A. Farooqui
  • Lloyd A. Horrocks


Galactosylceramides and sulfogalactosylceramides are characteristic lipids of the myelin sheath. Two genetically determined leukodystrophies are caused by an inability to enzymically hydrolyze these glycolipids. Thus, a deficiency of galactocerebroside β-galactosidase results in globoid cell leukodystrophy, whereas a reduced activity of arylsulfatase A is responsible for metachromatic leukodystrophy. Besides these disorders, deficiencies of arylsulfatases A, B, C, and other sulfatases have been shown in a distinct condition called “multiple sulfatase deficiency”. All of these disorders are fatal and are characterized by marked demyelination and severe mental retardation. The cause of this demyelination is not known. However, cytotoxic galactosylsphingosine and sulfogalactosylsphingosine have been suggested as the agents responsible for this demyelination. Recent immunological studies have also shown that patients with globoid and metachromatic leukodystrophies contain a mutant galactocerebroside β-galactosidase and arylsulfatase A, respectively. The mutant enzymes have different kinetic properties compared to the enzymes from normal subjects. However, the can cross-react with antibodies to these enzymes. Since partially purified preparations of galactocerebroside β-galactosidase and homogeneous arylsulfatase A are now available, the possibility of enzyme replacement therapy in globoid and metachromatic leukodystrophies is discussed.

Index Entries

Biochemistry, of the leukodystrophies leukodystrophies, the biochemistry of, globoid cell leukodystrophy, galactocerebroside β-galactosidase deficiency in leukodystrophy, globoid cell metachromatic leukodystrophy, arylsulfatase A deficiency in galactocerebroside β-galactosidase deficiency, in globoid cell leukodystrophy arylsulfatase A deficiency, in metachromatic leukodystrophy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alpers D. J. (1969) Separation and isolation of rat and human intestinal β-galactosidase.J. Biol. Chem. 244, 1237–1242.Google Scholar
  2. Aronson N. N. (1972) Degradation of Glycoproteins by Lysosomal Enzymes, inThe Glycoproteins Part B (Gottschalk A., ed.) pp. 1211–1232. Elsevier Publishing Co., Amsterdam.Google Scholar
  3. Austin J. H. (1959) Metachromatic sulfatides in cerebral white matter and kidney.Proc. Soc. Exp. Biol. 100, 361–364.PubMedGoogle Scholar
  4. Austin J. H., Balasubramanian A. S., Pattabiraman T. N., Saraswathi S., Basu D. K., and Bachhawat B. K. (1963) A controlled study on enzymic activities in three human disorders of glycolipid metabolism.J. Neurochem. 10, 805–816.PubMedCrossRefGoogle Scholar
  5. Austin J., McAfee D., Shearer L., and Ore P. (1965) Metachromatic forms of diffuse cerebral sclerosis.Arch. Neurol. 12, 447–455.PubMedGoogle Scholar
  6. Austin J. H. (1967) Some recent findings in leukodystrophies and in gargoylism. inInborn Disorders of Sphingolipid Metabolism (Aronson S. N. and Volk B. W., eds.) pp. 359–387. Pergamon Press, New York.Google Scholar
  7. Austin J., Suzuki K., Armstrong D., Brady R., Bachhawat B. K., and Stumpf D. (1970) Studies on globoid (Krabbe) leukodystrophy.Arch. Neurol. 23, 502–512.PubMedGoogle Scholar
  8. Austin J. H. (1973) Multiple sulfatase deficiency.Arch. Neurol. 28, 258–264.PubMedGoogle Scholar
  9. Avila J. A. and Convit J. (1976) Physiocochemical characteristics of the glycosaminoglycans-lysosomal enzyme interaction in vitro.Biochem. J. 160, 129–135.PubMedGoogle Scholar
  10. Bach G., Eisenberg F., Cantz M., and Neufeld E. F. (1973) The defect in the Hunter syndrome: deficiency of sulfoiduronate sulratase.Proc. Natl. Acad. Sci. USA 70, 2134–2138.PubMedCrossRefGoogle Scholar
  11. Bachhawat B. K., Austin J., and Armstrong D. A. (1967) A cerebroside sulfotransferase deficiency in a human disorder of myelin.Biochem. J. 104, 15C-17C.Google Scholar
  12. Balasubramanian K. A. and Bachhawat B. K. (1975) Purification, properties and glycoprotein nature of arylsulfatase A from sheep brain.Biochim. Biophys. Acta 403, 113–121.PubMedGoogle Scholar
  13. Barranger J. A., Rapoport S. I., Fredericks W. R., Pentchev P. G., MacDermat K. D., Steusing J. K., and Brady R. O. (1979) Modification of the blood-brain barrier: Increased concentration and fate of enzyme entering the brain.Proc. Natl. Acad. Sci. USA 76, 481–485.PubMedCrossRefGoogle Scholar
  14. Basner R., Von-Figura K., Glossl J., Klein U., Kresse H., and Mlekusch W. L. (1979) Multiple deficiency of mucopolysaccharide sulfatases in mucosulfatidosis.Pediatr. Res. 13, 1316–1318.PubMedCrossRefGoogle Scholar
  15. Benson P. F. (1982) Treatment of the mucopolysaccharidoses by fibroblast or bone marrow transplantation.Prog. Clin. Biol. Res. 103, 597–599.PubMedGoogle Scholar
  16. Ben-Yoseph Y., Hungerford M., and Nadler H. L. (1978) The nature of mutation in Krabbe disease.Am. J. Hum. Genet. 30, 644–652.PubMedGoogle Scholar
  17. Ben-Yoseph Y., Hungerford M., and Nadler H. L. (1979) Galactosylceramide β-galactosidase in Krabbe Disease: Partial purification and characterization of the mutant enzyme.Arch. Biochem. Biophys. 196, 93–101.PubMedCrossRefGoogle Scholar
  18. Ben-Yoseph Y., Hungerford M., and Nadler H. L. (1980) The interrelations between high and low molecular-weight forms of normal and mutant (Krabbe Disease) galactocerebrosidase.Biochem. J. 189, 9–15.PubMedGoogle Scholar
  19. Besley G. T. N. and Bain A. D. (1978) Use of a chromogenic substrate for the diagnosis of Krabbe’s disease with special reference to its application in prenatal diagnosis.Clin. Chim. Acta. 88, 229–236.PubMedCrossRefGoogle Scholar
  20. Besley G. T. N. and Gatt S. (1981) Spectrophotometric and fluorimetric assays of galactocerebrosidase activity, their use in the diagnosis of Krabbe’s disease.Clin. Chim. Acta 110, 19–26.PubMedCrossRefGoogle Scholar
  21. Bishayee S., Farooqui A. A., and Bachhawat B. K. (1973) Purification of brain lysosomal arylsulfatases by concanavalin A Sepharose column chromatography.Ind. J. Biochem. Biophys. 10, 1–2.Google Scholar
  22. Bowen D. M. and Radin N. S. (1968) Purification of cerebroside galactosidase from rat brain.Biochim. Biophys. Acta 152, 587–598.PubMedGoogle Scholar
  23. Brady R. O. and Barranger J. A. (1982) The therapeutic strategies for lipid storage diseases.Trends Neurosci. 4, 265–267.CrossRefGoogle Scholar
  24. Brady R. O. (1983) Lysosomal storage diseases.Pharmac. Ther. 19, 327–336.CrossRefGoogle Scholar
  25. Breslow J. L. and Sloan H. R. (1972) Purification of arylsulfatase A from human urine.Biochem. Biophys. Res. Commun. 46, 919–925.PubMedCrossRefGoogle Scholar
  26. Bruns G. A. D., Leary A. C., Regina V. M., and Geraid P. S. (1978) Expression of human arylsulfatase A in man-hamster somatic cell hybrid.Cytogenet. Cell. Genet. 22, 182–185.PubMedGoogle Scholar
  27. Butterworth J., Broadhead D. M., and Keay A. J. (1978) Low arylsulfatase A activity in a family without metachromatic leukodystrophy.Clin. Genet. 14, 213–218.PubMedCrossRefGoogle Scholar
  28. Chang P. L. and Davidson R. G. (1980) Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts.Proc. Natl. Acad. Sci. USA 77, 6166–6170.PubMedCrossRefGoogle Scholar
  29. Chang T. M. S. (1964) Semipermeable microcapsules.Science 146, 524–526.PubMedCrossRefGoogle Scholar
  30. Chang T. M. S. (1973) Immobilization of enzymes, adsorbents or both within semipermeable microcapsules for clinical and experimental treatment of metabolite related disorders, inEnzyme Replacement for Genetic Diseases. (Desnick R. J., Bernlohr K., and Krivit W., eds.), pp. 66–75. Williams and Wilkins, Baltimore.Google Scholar
  31. Chwe A. Y. and Leslie S. E. (1983) Enhancement by sulfatide of Na+-independent [3H]GABA binding in mouse brain.Biochem. Biophys. Res. Commun. 112, 827–832.CrossRefGoogle Scholar
  32. Cho T. M., Cho S. C., and Loh H. H. (1976)3H-cerebroside sulfate redistribution induced by cation, opiate or phosphatidyl serine.Life Sci. 19, 117–124.PubMedCrossRefGoogle Scholar
  33. Colley C. M. and Ryman B. E. (1976) The liposome: from membrane model to the therapeutic agent.Trends Biochem. Sci. 1, 203–205.Google Scholar
  34. Collier J. and Greenfield J. G. (1924) The encephalitis periaxialis of Schilder: A clinical and pathological study with an account of two cases, one of which was diagnosed during life.Brain 47, 489–519.CrossRefGoogle Scholar
  35. Conzelmann E. and Sandhoff K. (1978) A B variant of infantile GM2 gangliosidosis: Deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside GM2 and glycolipid GA2.Proc. Natl. Acad. Sci. USA 75, 3979–3983.PubMedCrossRefGoogle Scholar
  36. Conzelmann E., Burg J., Stephan G., and Sandhoff K. (1982) Complexing of glycolipids and their transfer between membranes by the activator protein for degradation of lysosomal ganglioside GM-2.Eur. J. Biochem. 123, 455–464.PubMedCrossRefGoogle Scholar
  37. Crawfurd M. D. A. (1982) Review: Genetics of steroid sulfatase deficiency and X-linked ichthyosis.J. Inher. Metabo. Dis. 5, 153–163.CrossRefGoogle Scholar
  38. Cuzner M. L., Davison A. N., and Gregson N. A. (1965) The chemical composition of vertebrate myelin and microsomes.J. Neurochem. 12, 469–481.PubMedCrossRefGoogle Scholar
  39. Dean M. F., Steven, R. L., Muir H., Benson P. F., Button L. R., Anderson R. L., Boylston A., Mowbray J. (1979) Enzyme replacement therapy by fibroblast transplantation: long term biochemical study in three cases of Hunter’s disease.J. Clin. Invest. 63, 138–145.PubMedGoogle Scholar
  40. Dean M. F., Muir H., Benson P. F., and Button L. R. (1982) Effectiveness of HLA-compatible fibroblasts for enzyme replacement therapy in mucopolysaccharidoses.Pediatr. Res. 16, 260–261.PubMedCrossRefGoogle Scholar
  41. DeLuca C., Brown J. A., and Shows T. B. (1979) Lysosomal arylsulfatase deficiencies in human: chromosome assignments for arylsulfatases A and B.Proc. Natl. Acad. Sci. USA 76, 1957–1961.PubMedCrossRefGoogle Scholar
  42. Desnick R. J., Thorpe S. R., and Fiddler M. B. (1976) Toward enzyme therapy for lysosomal storage diseases.Physiol. Rev. 56, 57–99.PubMedGoogle Scholar
  43. Dickerman, L. H., Kurczynski, T. W., and MacBride, R. G. (1981) The effects of psychosine upon growth of human skin fibroblasts from patients with globoid cell leukodystrophy.J. Neurol. Sci. 50, 181–190.PubMedCrossRefGoogle Scholar
  44. Draper R. K., Fiskum G. M., and Edmond J. (1976) Purification, molecular weight, amino acid and subunit composition of arylsulfatase A from human liver.Arch. Biochem. Biophys. 177, 525–538.PubMedCrossRefGoogle Scholar
  45. Dubois G., Harzer K., and Baumann N. (1977) Very low arylsulfatase and cerebroside sulfatase activities in leukocytes of healthy members of MLD family.Am. J. Genet. 29, 191–194.Google Scholar
  46. Duchen L. W., Eicher E. M., Jacobs J. M., Scardvilli F., and Teixeira F. (1980) Hereditary leukodystrophy in the mouse: The new mutant twitcher.Brain 103, 695–710.PubMedCrossRefGoogle Scholar
  47. Dulaney J. T. and Moser H. W. (1978) Metachromatic Leukodystrophy, inMetabolic Basis of Inherited Diseases (Stanbury J. B., Wyngaarden J. B., and Fredrickson D. S., eds. pp. 770–809. McGraw-Hill, New York.Google Scholar
  48. Dunn H. G., Dolman C. L., Farrell D. F., Tischler B., Hasinoff C., and Woolf L. I. (1976) Krabbe’s leukodystrophy without globoid cells.Neurology 26, 1035–1041.PubMedGoogle Scholar
  49. Ebadi M. and Chweh A. (1980) Inhibition by arylsulfatase A of Na-independent (3H)-GABA and (3H)-muscimol binding to bovine cerebellar synaptic membranes.Neuropharmacology 19, 1105–1111.PubMedCrossRefGoogle Scholar
  50. Eto Y., Weismann U., and Herschkowitz N. N. (1974a) Sulfogalactosylsphingosine sulfatase. Characteristics of the enzyme and its deficiency in metachromatic leukodystrophy in human cultured skin fibroblasts.J. Biol. Chem. 249, 4955–4960.PubMedGoogle Scholar
  51. Eto Y., Rampini S., Weismann U., and Herschkowitz N. N. (1974b) Enzymic studies of sulfatases in tissues of the normal human and in metachromatic leukodystrophy with multiple sulfatase deficiencies.J. Neurochem. 23, 1161–1170.PubMedCrossRefGoogle Scholar
  52. Eto Y., Weismann U. N., Carson J. H., and Herschkowitz N. N. (1974c) Multiple sulfatase deficiencies in cultured skin fibroblasts.Arch. Neurol. 30, 153–156.PubMedGoogle Scholar
  53. Eto Y., Tokora T., Handa T., Herschkowitz N. N., and Rennert O. M. (1982) Acid mucopolysaccharide abnormality in multiple sulfatase deficiency: Chemical composition of AMPS in urine and liver.Pediatr. Res. 16, 395–399.PubMedCrossRefGoogle Scholar
  54. Eto Y., Tahara T., Tokoro T., and Malkawa K. (1983) Various sulfatase activities in leukocytes and cultured skin fibroblasts from heterozygotes for the multiple sulfatase deficiency.Pediatr. Res. 17, 97–100.PubMedCrossRefGoogle Scholar
  55. Fankhauser R., Lunginbuhl H., and Hartley W. J. (1963) Leukodystrophie vom Typus Krabbe beim Hund.Schweiz. Arch. Tierheilkd. 105, 198–207.Google Scholar
  56. Farooqui A. A. (1976) Purification and properties of human placenta arylsulfatase A.Arch. Int. Physiol. Biochim. 84, 479–492.PubMedCrossRefGoogle Scholar
  57. Farooqui A. A. (1980a) 3-Phosphoadenosine-5′-phosphosulfate metabolism in mammalian tissue.Int. J. Biochem. 12, 529–536.PubMedCrossRefGoogle Scholar
  58. Farooqui A. A. (1980b) Sulfatases, sulfate esters and their metabolic disorders.Clin. Chim. Acta. 100, 285–299.PubMedCrossRefGoogle Scholar
  59. Farooqui A. A. (1980c) Purification of enzymes by heparin-Sepharose chromatography.J. Chromatog. 184, 335–345.CrossRefGoogle Scholar
  60. Farooqui A. A. (1981) Metabolism of sulfolipid in mammalian tissues.Adv. Lipid Res. 18, 159–202.PubMedGoogle Scholar
  61. Farooqui A. A. and Bachhawat B. K. (1972) Purification and properties of arylsulfatase A from chicken brain.Biochem. J. 126, 1025–1033.PubMedGoogle Scholar
  62. Farooqui A. A. and Bachhawat B. K. (1973) Enzymatic desulfation of cerebroside 3-sulfate by chicken brain arylsulfatase A.J. Neurochem. 20, 889–891.PubMedCrossRefGoogle Scholar
  63. Farooqui A. A. and Mandel P. (1977a) Recent developments in the biochemistry of globoid and metachromatic leukodystrophies.Biomedicine 26, 232–236.PubMedGoogle Scholar
  64. Farooqui A. A. and Mandel P. (1977b) On properties and role of arylsulfatases A, B and C in mammals.Int. J. Biochem. 8, 685–691.CrossRefGoogle Scholar
  65. Farooqui A. A. and Srivastava P. N. (1979) Isolation, characterization and the role of rabbit testicular arylsulfatase A in fertilization.Biochem. J. 181, 331–337.PubMedGoogle Scholar
  66. Farooqui A. A., Rebel G., and Mandel P. (1977) Sulfatide metabolism in brain.Life Sci. 20, 569–583.PubMedCrossRefGoogle Scholar
  67. Farooqui A. A. and Horrocks L. A. (1984) Heparin-Sepharose affinity chromatography.Adv. Chromatog. 23, 127–148.Google Scholar
  68. Farrell D. F., MacMartin M. P., and Clark A. F. (1979) Multiple molecular forms of arylsulfatase A in different forms of metachromatic leukodystrophy (MLD).Neurology 29, 16–20.PubMedGoogle Scholar
  69. Fischer G. and Jatzkewitz H. (1975) The activator of cerebroside sulphatase. Purification from human liver and identification as a protein.Hoppe-Seyler’s Z. Physiol. Chem. 356, 605–613.PubMedGoogle Scholar
  70. Fischer G. and Jatzkewitz H. (1975) The activator of cerebroside sulfatase: A model of the activation.Biochim. Biophys. Acta 528, 69–76.Google Scholar
  71. Fletcher T. F., Suzuki K., and Martin F. (1977) Galatocerebrosidase activities in canine globoid leukodystrophy.Neurology 27, 758–767.PubMedGoogle Scholar
  72. Fluharty A. L., Stevens R. L., Miller R. T., and Kihara H. (1974) Sulfoglycerogalactolipid from rat testes: A substrate for pure human arylsulfatase A.Biochem. Biophys. Res. Commun. 61, 348–354.PubMedCrossRefGoogle Scholar
  73. Fluharty A. L., Stevens R. L., Miller R. T., Shapiro S. S., and Kihara H. (1976) Ascorbic acid 2-sulfate sulfohydrolase activity of human arylsulphatase A.Biochim. Biophys. Acta 429, 508–516.PubMedGoogle Scholar
  74. Fluharty A. L., Stevens R. L., Goldstein E. B., and Kihara H. (1979a) The activity of arylsulfatases A and B on tyrosineO-sulfates.Biochim. Biophys. Acta 566, 321–326.PubMedGoogle Scholar
  75. Fluharty A. L., Stevens R. L., Delaflor S. D., Shapiro L. J., and Kihara H. (1979b) Arylsulfatase A modulation with pH in multiple sulfatase deficiency disorder fibroblasts.Am. J. Hum. Genet. 31, 574–580.PubMedGoogle Scholar
  76. Fluharty A. L., Stevens R. L., Miller R. T., and Kihara H. (1980) Bile salt activation of cerebroside sulfate sulfohydrolase.Biochem. J. 189, 45–49.PubMedGoogle Scholar
  77. Fluharty A. L., Meek W. E., and Kihara H. (1983) Pseudoarylsulfatase deficiency: Evidence for a structurally altered enzyme.Biochem. Biophys. Res. Commun. 112, 191–197.PubMedCrossRefGoogle Scholar
  78. Flynn T. J., Deshmukh D. S., Subba Rao G., and Pieringer R. A. (1975) Sulfogalactosyl diacylglycerol: Occurrence and biosynthesis of a novel lipid in rat brain.Biochem. Biophys. Res. Commun. 65, 122–128.PubMedCrossRefGoogle Scholar
  79. France J. T. and Liggins G. C. (1969) Placental sulfatase deficiency.J. Clin. Endocrinol. 29, 138–141.Google Scholar
  80. France J. T., Seddon R. J., and Ligging G. E. (1973) A study of a pregnancy with low oestrogen production due to placental sulfatase deficiency.J. Clin Endocrinol. 36, 1–9.Google Scholar
  81. Gal A. E., Brady R. O., Pentchev P. G., Furbish F. S., Suzuki K., Tanaka H., and Schneider E. L. (1977) A practical chromogenic procedure for the diagnosis of Krabbe’s disease.Clin. Chim. Acta 77, 53–59.PubMedCrossRefGoogle Scholar
  82. Gartner S. Conzelmann E., and Sandhoff K. (1983) Activator protein for the degradation of globotriaosylceramide by human β-galactosidase.J. Biol. Chem. 258, 12378–12385.PubMedGoogle Scholar
  83. Gatt S. (1967) Enzymatic hydrolysis of sphingolipids V. Hydrolysis of monosialoganglioside and hexosylceramides by rat brain β-galactosidase.Biochim. Biophys. Acta 137, 192–194.PubMedGoogle Scholar
  84. Greene H. L., Hug G., and Schubert W. K. (1969) Metachromatic leukodystrophy: Treatment with arylsulfatase A.Arch. Neurol. (Chic). 20, 147–153.Google Scholar
  85. Gregoriadis G. (1980) Liposome Drug Carrier Concept: Its Development and Future, inLipsosomes in Biological Systems (Gregoriadis G. and Allison C. A., eds), pp. 25–86. Wiley, New York.Google Scholar
  86. Hahn A. F., Gordon B. A., Gilbert J. J., and Hinton G. G. (1981) The AB-variant of metachromatic leukodystrophy (Postulated activator protein deficiency).Acta Neuropathol. 55, 281–287.PubMedCrossRefGoogle Scholar
  87. Hansson C. G., Karlsson K. A., and Samuelsson B. E. (1978) The identification of sulfatides in human erythrocyte membrane and their relation to Na+-K+ dependent ATPase.J. Biochem. (Tokyo) 83, 813–819.Google Scholar
  88. Harben A. M., Krawiecki N., Marcus R., and Hommes F. A. (1982) AK m mutant of arylsulfatase A.Clin. Chim. Acta 125, 351–354.PubMedCrossRefGoogle Scholar
  89. Hechtman P., Gordon B. A., and Kim N. G. Y. (1982) Deficiency of the hexosaminidase A activator protein in a case of GM2-gangliosidosis: Variant AB.Pediatr. Res. 16, 217–222.PubMedGoogle Scholar
  90. Helwig J. J., Farooqui A. A., Bollock C., and Mandel P. (1977) Purification and some properties of arylsulfatases A and B from rabbit kidney cortex.Biochem. J. 165, 127–134.PubMedGoogle Scholar
  91. Ho M. W. and O’Brien J. S. (1971) Gaucher disease: Deficiency of “acid” β-glucosidase and reconstitution of enzyme activityin vitro.Proc. Natl. Acad. Sci. USA 68, 2810–2813.PubMedCrossRefGoogle Scholar
  92. Hobbs J. R., Hugh-Jones K., Barett A. J., Byrom N., Chambers D., Henry K., James D. C. O., Lucas C. F., Rogers T. R., Benson P. F., Tansley L. R., Mossman J., Young E. P., and Patrick A. D. (1981) Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation.Lancet II, 709–712.CrossRefGoogle Scholar
  93. Hoogeveen A. T., Verheijen F. W., and Galjaard H. (1983) The relation between human lysosomal β-galactosidase and its protective protein.J. Biol. Chem. 258, 12145–12146.Google Scholar
  94. Hors-Cayla M. C., Heuertzs S., Van Cong N., Weil D., and Frezal J. (1979) Confirmation of the assignment of the gene for arylsulfatase A to chromosome 22 using somatic cell hybrids.Hum. Genet. 49, 33–40.PubMedGoogle Scholar
  95. Horwitz A. L. (1979) Genetic complementation studies of multiple sulfatase deficiency.Proc. Natl. Acad. Sci. USA 76, 6499–6499.CrossRefGoogle Scholar
  96. Ihler G. M., Glew R. H., and Schnure F. W. (1973) Enzyme loading of erythrocytes.Proc. Natl. Acad. Sci. USA 70, 2663–2666.PubMedCrossRefGoogle Scholar
  97. Igisu H., Takahashi H., Suzuki K., and Suzuki K. (1983) Abnormal accumulation of galactosylceramide in the kidney of twitcher mouse.Biochem. Biophys. Res. Commun. 110, 940–944.PubMedGoogle Scholar
  98. Igisu H. and Suzuki K. (1984) Glycolipids of the spinal cord, sciatic nerve and systemic organs of the twitcher mouse.J. Neuropath. Expt. Neurol. 43, 22–26.Google Scholar
  99. Inui K. and Wenger D. A. (1982) Properties of a protein activator of glycosphingolipid hydrolysis isolated from the liver of a patient with GM-1 gangliosidosis type I.Biochem. Biophys. Res. Commun. 105, 745–751.PubMedGoogle Scholar
  100. Inui K. and Wenger D. A. (1983) Concentrations of an activator protein for sphingolipid hydrolysis in liver and brain samples from patients with lysosomal storage diseases.J. Clin. Invest. 72, 1622–1625.PubMedGoogle Scholar
  101. Inui, K., Emmett, M., and Wenger, D. A. (1983) Immunological evidence for deficiency in an activator protein for sulfatide sulfatase in a variant form of metachromatic leukodystrophy.Proc. Natl. Acad. Sci. USA 80, 3074–3077.PubMedCrossRefGoogle Scholar
  102. Ishibashi T., Maru A., Imai Y., Makita A., and Tsuji I. (1980) A varient form of arylsulfatase A in human urine derived from the renal pelvis.Biochim. Biophys. Acta 616, 218–227.PubMedGoogle Scholar
  103. Ishizuka I., Inomata M., Ueeno K., and Yamakawa T. (1978) Sulfated glyceroglycolipid in rat brain. Structure, sulfationin vivo and accumulation in whole brain during development.J. Biol. Chem. 253, 898–907.PubMedGoogle Scholar
  104. James G. T. and Austin J. H. (1979) Studies in metachromatic leukodystrophy XIV. Purification and subunit structure of human liver arylsufatase A.Clin. Chim. Acta 98, 103–111.PubMedCrossRefGoogle Scholar
  105. Jatzkewitz H. (1958) Zwei Typen von Cerebrosid-Schwefelsaureestern als sog. Paralipoide and Speichersubstanzen bei der Leukodystrophie, Typ Scholz (Metachromatische Form der diffusen Skelerose).Hoppe-Seylers Z. Physiol. Chem. 311, 279–282.PubMedGoogle Scholar
  106. Jatzkewitz H. (1978) Existence localization and some properties of the activators of sphingolipid hydrolases.Adv. Exp. Med. Biol. 101, 561–571.PubMedGoogle Scholar
  107. Jerfy A. and Roy A. B. (1973) Comparison of the arylsulfatase and cerebroside sulfatase activities of sulfatase A.Biochim. Biophys. Acta. 293, 178–190.PubMedGoogle Scholar
  108. Johnson K. H. (1970) Globoid leukodystrophy in the cat.J. Am. Vet. Med. Assoc. 157, 2057–2064.PubMedGoogle Scholar
  109. Kihara H. (1982) Genetic heterogeneity in metachromatic leukodystrophy.Am. J. Hum. Genet. 34, 171–181.PubMedGoogle Scholar
  110. Kobayashi T., Yamanaka T., Jacobs J. M., Teixeira F., and Suzuki K. (1980) The Twitcher mouse an emzymatically authentic model of human globoid cell leudodystrophy.Brain Res. 202, 479–483.PubMedCrossRefGoogle Scholar
  111. Kobayashi T. and Suzuki K. (1982) The twitcher mouse: Fate of exogenously administered [3H]galactosylsphingosine.Adv. Expt. Med. Biol. 152, 253–259.Google Scholar
  112. Kolodny E. H. and Moser H. W. (1983) Sulfatide Lipidosis: Metachromatic Leukodystrophy, inThe Metabolic Basis of Inherited Diseases (Stanbury J. B., Wyngaarden J. B., Fredrickson D. S., Goldstein J. L., and Brain M. S. eds.), pp. 881–905. McGraw-Hill, New York.Google Scholar
  113. Kosugi M., Maru A., Mitsuhashi K., Koyanagi T., Ishibashi T., and Imai Y. (1983) Clinical significance of a variant form of urinary arylsulfatase A.Jap. J. Exp. Med. 53, 73–76.PubMedGoogle Scholar
  114. Kresse H. and Holtfrerich D. (1980) Thiosulfate-mediated increase of arylsulfatase activities in multiple sulfatase deficiency disorder fibroblasts.Biochem. Biophys. Res. Commun. 97, 41–48.PubMedCrossRefGoogle Scholar
  115. Lagenbeck U., Dunker P., Heipertz P., and Pilz H. (1977) Inheritance of metachromatic leukodystrophy.Am. J. Hum. Genet. 29, 639–640.Google Scholar
  116. Lee M. B., Sapirstein V. S., Reiss D. S., and Kolodny E. H. (1980) Carbonic anhydrase and 2′,3′ cyclic nucleotide 3′-phosphohydrolase activity in normal human brain and in demyelinating diseases.Neurology 30, 719–727.Google Scholar
  117. Li S. C. and Li Y. T. (1976) An activator stimulating the enzymic hydrolysis of sphingoglycolipids.J. Biol. Chem. 251, 1159–1163.PubMedGoogle Scholar
  118. Li S. C., Nakamura T., Ogamo A., and Li Y-T. (1979) Evidence for the presence of two separate protein activators for the enzymic hydrolysis of GM-1 and GM-2 ganglioside.J. Biol. Chem. 254, 10592–10595.PubMedGoogle Scholar
  119. Li Y. T. and Li S. C. (1983) Activator Proteins for Sphingolipid Hydrolysis, inThe Enzymes (Boyer P. D., ed.), pp. 427–445. Academic Press, New York.Google Scholar
  120. Loh H. H., Law P. Y., Ostwald T., Cho T. M., and Way E. L. (1978) Possible involvement of cerebroside sulfate in opiate receptor binding.Fed. Proc. 37, 147–152.PubMedGoogle Scholar
  121. Lott I. T., Dulaney J. T., Milunsky A., Hoefnagel D., and Moser H. W. (1976) Apparent biochemical homozygosity in two obligatory heterozygotes of metachromatic leukodystrophy.J. Pediatr. 89, 483–440.CrossRefGoogle Scholar
  122. Luijten J. A. F. M., Heijden M. C. M. V., Rijksen G., and Staal G. E. J. (1978a) Purification and characterization of arylsulfatase A from human urine.J. Mol. Med. 3, 213–225.Google Scholar
  123. Luijten J. A. F. M., Heijden M. C. M. V., Rijksen G., Willemse J., and Staal G. E. J. (1978b) Characterization of arylsulfatase A of three cases of metachromatic leukodystrophy: One of the late infantile, one of the juvenile and one of the adult variant.J. Mol. Med. 3, 227–246.Google Scholar
  124. Martensson E. (1963) On the sulfate containing lipids of human kidney.Acta Chem. Scand. 17, 1174–1176.Google Scholar
  125. Martensson E. (1966) Sulfatide of human kidney: Isolation, identification and fatty acid composition.Biochim. Biophys. Acta 116, 521–531.PubMedGoogle Scholar
  126. Mehl E. and Jatzkewitz H. (1964) Eine Cerebrosidulfatase aus Schweineniere.Hoppe-Seyler’s Z. Physiol. Chem. 339, 260–276.PubMedGoogle Scholar
  127. Mehl E. and Jatzkewitz H. (1968) Cerebroside 3-sulfate as a physiological substrate of arylsulfatase A.Biochim. Biophys. Acta 151, 619–627.PubMedGoogle Scholar
  128. Miyatake T. and Suzuki K. (1972) Globoid cell leukodystrophy: Additional deficiency of psychosine galactosidase.Biochem. Biophys. Res. Commun. 48, 538–543.CrossRefGoogle Scholar
  129. Miyatake T. and Suzuki K. (1975) Partial purification and characterization of β-galactosidase from rat brain hydrolysing glycosphingolipids.J. Biol. Chem. 250, 585–590.PubMedGoogle Scholar
  130. Mohandas T., Shapiro L. J., Sparkes R. S., and Sparkes M. C. (1979) Regional assignment of the steroid sulfatase-X linked ichthyosis locus.Proc. Natl. Acad. Sci. USA 76, 5779–5783.PubMedCrossRefGoogle Scholar
  131. Munnich A., Saudubray J. M., Hors-Cayla M. C., Poenaru L., Ogier H., Strecker G., Aicardi J., Frezal J., and Maroteaux P. (1982) Enzyme replacement therapy by transplantation of HLA-compatible fibroblasts in Sanfilippo syndrome: Another trial.Pediatr. Res. 16, 259–261.PubMedCrossRefGoogle Scholar
  132. Murphy J. V., Wolfe H. J., Balaz E. A., and Moser H. (1971) A patient with deficiency of arylsulfatase A,B,C, and steroid sulphatase associated with storage of sulfatide, cholesterol and glycosaminoglycans inLipid Storage Diseases (Bernsohn J. and Gossman J., eds.), pp. 67–110. Academic Press, New York.Google Scholar
  133. Naoi M. and Yagi K. (1980) Incorporation of enzyme through blood-brain barrier into brain by means of liposomes:Biochem. Int. 1, 591–596.Google Scholar
  134. Navari R. M., Buckner C. D., Clift R. A., and Coleman K. M. (1984) Bone Marrow Transplantation,Lab. Med. 15, 245–250.Google Scholar
  135. Neuwelt E. A., Barranger J. A., Brady R. O., Pagel M., Furbish F. S., Quirk J. M., Mook G. E., and Frenkel E. (1981) Delivery of hexosaminidase A to the cerebrum after osmotic modification of the blood-brain barrier.Proc. Natl. Acad. Sci. USA 78, 5838–5841.PubMedCrossRefGoogle Scholar
  136. Norton W. T. (1981) Biochemistry of Myelin in Demyelinating Diseases:Basic and Clinical Electrophysiology (Waxman S. G. and Ritchie J. M., eds.) pp. 93–121. Raven Press, New York.Google Scholar
  137. Nussbaum J. L. and Mandel P. (1972) Enzymic synthesis of psychosine sulfate.J. Neurochem. 19, 1789–1802.PubMedCrossRefGoogle Scholar
  138. Oakey R. E. (1978) Placental sulfatase deficiency: antepartum differential diagnosis from foetal hypoplasia.Clin. Endocrinol. 9, 81–88.Google Scholar
  139. Oakey R. E., Cawood M., and MacDonald R. R. (1984) Biochemical and clinical observations in a pregnancy with placental sulfatase and other enzyme deficiencies.Clin. Endocrinol. 3, 131–148.Google Scholar
  140. O’Brien J. S. and Sampson E. L. (1965) Myelin membrane: A molecular abnormality.Science 150, 1613–1617.PubMedCrossRefGoogle Scholar
  141. Okada S. and O’Brien J. S. (1968) Generalized gangliosidosis: β-Galactosidase deficiency.Science 160, 1002–1004.PubMedCrossRefGoogle Scholar
  142. Okada S., Kato T., Yabuuchi H., Yoshino K., Naoi M., Kiuchi K., and Yagi K. (1984) Use of a fluorescent analogue of galactocerebroside for assay of galactocerebroside β-galactosidase activity in skin fibroblasts from patients with Krabbe’s disease.Clin. Chim. Acta 136, 57–63.PubMedCrossRefGoogle Scholar
  143. Onodera H., Takada G., Tada K., and Desnick R. J. (1983) Microautoradiographic study on the tissue localization of liposome-entrapped or unentrapped3H-labeled β-galactosidase injected into rats.Tohoku J. Exp. Med. 140, 1–13.PubMedGoogle Scholar
  144. Poduslo S. E., Tennekoon G., Price D., Miller K., and McKhann G. M. (1976) Fetal metachromatic leukodystrophy: Pathology, biochemistry and a study ofin vitro enzyme replacement in CNS tissue.J. Neuropath. Expt. Neurol. 35, 622–632.Google Scholar
  145. Porter, M. T., Fluharty A. L., Trammell J., and Kihara H. (1971a) A correlation of intracellular cerebroside sulfatase activity in fibroblasts with latency in metachromatic leukodystrophy.Biochem. Biophys. Res., Commun. 44, 660–666.CrossRefGoogle Scholar
  146. Porter M. T., Fluharty A. L., and Kihara H. (1971b) Correction of abnormal cerebroside sulfate metabolism in cultured metachromatic leukodystrophy fibroblasts.Science 172, 1263–1265.PubMedCrossRefGoogle Scholar
  147. Porter M. T., Fluharty A. L., DelaFlor, S. D., and Kihara H. (1972) Cerebroside sulfate determination in human fibroblast.Biochim. Biophys. Acta 258, 769–778.PubMedGoogle Scholar
  148. Pritchard D. H., Napthine D. V., and Sinclair A. J. (1980) Globoid cell leukodystrophy in polled dorset sheep.Vet. Path. 17, 399–405.CrossRefGoogle Scholar
  149. Rattazzi M. C., Lanse S. B., McCullough R. A., Nester J. A., and Jacobs E. A. (1980) Towards enzyme replacement in GM2 gangliosidosis, inEnzyme Therapy in Genetic Disease (Desnick R. J., Paul N. W., and Dickman F., eds.) pp. 179–193. Liss, New York.Google Scholar
  150. Rattazzi M. C., Appel, A. M., Baker H. J., and Nester J. (1981) Towards Enzyme Replacement in GM2 Gangliosidosis, inLysosomes and Lysosomal Storage Diseases (Callahan J. W. and Lowden J. A., eds.), pp. 527–537. Raven Press, New York.Google Scholar
  151. Rose F. A. (1982) The mammalian sulfatases and placental sulfatase deficiency in man.J. Inher. Metab. Dis. 5, 145–152.PubMedCrossRefGoogle Scholar
  152. Sarafian T. A., Fluharty A. L., Kihara H., Helfand G., and Edmond J. (1982) Large scale purification of pyrogen-free human arylsulfatase A.J. Appl. Biochem. 4, 126–132.Google Scholar
  153. Scaravilli F. and Jacobs J. M. (1981) Peripheral nerve grafts in hereditary leukodystrophic mutant mice (twitcher).Nature 290, 56–58.PubMedCrossRefGoogle Scholar
  154. Scaravilli F. and Jacobs J. M. (1982) Improved myelination in nerve grafts from the leucodystrophic twitcher into trembler mice: Evidence for enzyme replacement.Brain Res. 237, 163–172.PubMedCrossRefGoogle Scholar
  155. Shapira E. and Nadler H. L. (1975a) The nature of the residual arylsulfatase activity in metachromatic leukodystrophy.J. Pediatr. 86, 881–882.PubMedCrossRefGoogle Scholar
  156. Shapira E. and Nadler H. L. (1975b) Purification and some properties of soluble human liver arylsulfatases.Arch. Biochem. Biophys. 170, 179–187.PubMedCrossRefGoogle Scholar
  157. Shapiro L. J., Cousins L., Fluharty A. L., Stevens R. L. and Kihara H. (1977) Steroid sulfatase deficiency.Pediat. Res. 11, 894–897.PubMedGoogle Scholar
  158. Shapiro L. J., Weiss R., Buxman M. M., Vidgoff J. Dimond R. L., Roller J. A. and Wells R. S. (1978) Enzymatic basis of typicalX-linked ichthyosis.Lancet 2, 756–757.PubMedCrossRefGoogle Scholar
  159. Shapiro L.J., Aleck K. A., Kaback M. M., Itabashi H., Desnick R. J., Brand N., Stevens R. L., Fluharty A. L., and Kihara H. (1979) Metachromatic leukodystrophy without arylsulfatase A deficiency.Pediatr. Res. 13, 1179–1181.PubMedCrossRefGoogle Scholar
  160. Stevens R. L., Hartman M., Fluharty A. L., and Kihara H. (1973) A second form of arylsulfatase A in human urine.Biochim. Biophys. Acta 302, 338–344.PubMedGoogle Scholar
  161. Stevens, R. L., Fluharty A. L., Skokut M. H., and Kihara H. (1975) Purification and properties of arylsulfatase A from human urine.J. Biol. Chem. 250, 2495–2501.PubMedGoogle Scholar
  162. Stevens R. L., Fluharty A. L., Killgrove A. R., and Kihara H. (1976) Microheterogeneity of arylsulfatase A from human tissues.Biochim. Biophys. Acta 445, 661–671.PubMedGoogle Scholar
  163. Stevens R. L., Fluharty A. L., Kihara H., Kaback M. M., Shapiro L. J., Marsh B., Sandhoff K., and Fischer G. (1981) Cerebroside sulfatase activator deficiency induced metachromatic leukodystrophy.Am. J. Hum. Genet. 33, 900–906.PubMedGoogle Scholar
  164. Stoffyn P. and Stoffyn A. (1963) Structure of sulfatide.Biochim. Biophys. Acta 70, 218–220.PubMedCrossRefGoogle Scholar
  165. Stumpf D., Neuwelt E., Austin J., and Kohler P. (1971) Metachromatic leukodystrophy (MLD) X. Immunological studies of the abnormal sulfatase A.Arch. Neurol. Chic. 25, 427–431.Google Scholar
  166. Stumpf D. and Austin J. (1971) Metachromatic leukodystrophy (MLD) IX. Qualitative and quantitative difference in urinary arylsulfatase A in different forms of MLD.Arch. Neurol. 24, 117–124.PubMedGoogle Scholar
  167. Subba Rao G., Narcia L. N., Pieringer J., and Pieringer R. A. (1977) The biosynthesis of sulfogalactosyldiacylglycerol of rat brainin vitro.Biochem. J. 166, 429–435.Google Scholar
  168. Suzuki Y. and Mizuno Y. (1974) Juvenile metachromatic leukodystrophy: Deficiency of an arylsulfatase A component.J. Pediatr. 85, 824–825.Google Scholar
  169. Suzuki Y. and Suzuki K. (1971) Krabbe’s globoid cell leukodystrophy: Deficiency of galactocerebrosidase in serum, leukocytes and fibroblasts.Science 171, 73–75.PubMedCrossRefGoogle Scholar
  170. Suzuki Y. and Suzuki K. (1974) Sphingolipid β-galactosidase: Electrofocusing characterization of the enzymes in human globoid cell leukodystrophy (Krabbe’s disease).J. Biol. Chem. 249, 2105–2108.PubMedGoogle Scholar
  171. Suzuki K. and Suzuki Y. (1983) Galactosylceramide Lipidosis: Globoid Cell Leucodystrophy, inMetabolic Basis of Inherited Diseases (Stanbury J. B., Wyngaarden J. B., Fredrickson D. S., Goldstein J. L., and Brown M. S., eds., pp. 857–880. McGraw-Hill, New York.)Google Scholar
  172. Suzuki K., Schneider E. L., and Epstein C. J. (1971)In utero diagnosis of globoid cell leukodystrophy (Krabbe’s disease).Biochem. Biophys. Res. Commun. 45, 1363–1366.PubMedCrossRefGoogle Scholar
  173. Svennerholm L. (1963) Some Aspects of the Biological Changes in Leukodystrophy, inBrain Lipids and Lipoproteins and Leukodystrophics, pp. 104–109, Elsevier, Amsterdam.Google Scholar
  174. Svennerholm L., Vanier M., and Mansson J. (1980) Krabbe’s disease: a galactosphingosine (psychosine) lipidosis.J. Lipid Res. 21, 53–64.PubMedGoogle Scholar
  175. Takada G., Onadera H., and Tada K. (1982) Delivery of fungal α-galactosidase to rat brain by means of liposomes.Tohoku J. Exp. Med. 136, 219–230.PubMedGoogle Scholar
  176. Takahashi H., Igisu H., Suzuki K., and Suzuki K. (1983) The twitcher mouse: An ultrastructural study on the oligodendroglia.Acta Neuropath. 59, 159–166.PubMedCrossRefGoogle Scholar
  177. Takahashi H. and Suzuki K. (1984) Demyelination in the spinal cord of murine globoid cell leukodystrophy (The twitcher mouse).Acta Neuropath. 62, 298–308.PubMedCrossRefGoogle Scholar
  178. Taketomi T. and Nishimura K. (1964) Physiological activity of psychosine.Jap. J. Exp. Med. 34, 255–265.PubMedGoogle Scholar
  179. Taori G. M., Mammen K. C., Kokrady S., Martin B., Bhaktaviziam A., and Bachawat B. K. (1970) Globoid leukodystrophy (Krabbe’s disease).Ind. J. Med. Res. 58, 993–1001.Google Scholar
  180. Tyrrell D. A., Heath T. D., Colley C. M., and Ryman B. E. (1976) New aspects of liposomes.Biochim. Biophys. Acta 457, 259–302.PubMedGoogle Scholar
  181. Uchida T., Egami F., and Roy A. B. (1981) 3′, 5′-cyclic nucleotide phosphodiesterase activity of the sulfatase A of ox liver.Biochim. Biophys. Acta 657, 356–363.PubMedGoogle Scholar
  182. Vanier M. T. and Svennerholm L. (1975) Chemical pathology of Krabbe’s disease III. Ceramide and ganglioside of brain.Acta Paediatr. Scand. 64, 641–648.PubMedCrossRefGoogle Scholar
  183. Vanier M. and Svennerholm L. (1976) Chemical pathology of Krabbe’s disease. The occurrence of psychosine and other neutral sphingoglycolipids inCurrent Trends in Sphingolipidoses and Allied Disorders (Volk B. W. and Schneck L., ed.), pp. 115–126, Plenum, New York.Google Scholar
  184. Waheed A., Hasilik A., and Von-Figura K. (1982) Enhanced breakdown of arylsulfatase A in multiple sulfatase deficiency.Eur. J. Biochem. 123, 317–321.PubMedCrossRefGoogle Scholar
  185. Waheed A., Steckel F., Hasilik A., and Von-Figura K. (1983) Two allelic forms of human arylsulfatase A with different numbers of asparagin-linked oligosaccharides.Am. J. Hum. Genet. 35, 228–233.PubMedGoogle Scholar
  186. Weismann U., Rossi E., Herschkowitz N. (1972) Correction of defective sulfatide degradation in cultured fibroblasts from patients with metachromatic leukodystrophy.Acta. Pediatr. Scand. 61, 296–302.CrossRefGoogle Scholar
  187. Wenger D. A., Sattler M., and Hiatt W. (1974) Globoid cell leukodystrophy: Deficiency of lactosylceramide β-galactosidase.Proc. Natl. Acad. Sci. USA 71, 854–857.PubMedCrossRefGoogle Scholar
  188. Wenger D. A., Sattler M., and Marley S. P. (1973) Deficiency of monogalactosyl diglyceride in Krabbe’s disease.Biochem. Biophys. Res. Commun. 53, 680–685.PubMedCrossRefGoogle Scholar
  189. Winchester B. (1982) Animal models of human genetic diseases.Trends Biochem. Sci. 7, 71–74.CrossRefGoogle Scholar
  190. Yamakawa T., Kiso N., Handa S., Makita A., and Yokoyama S. (1962) On the structure of brain cerebroside sulfuric ester and ceramide dihexoside of erythrocyte.J. Biochem. (Tokyo) 52, 266–227.Google Scholar

Copyright information

© The Humana Press Inc. 1984

Authors and Affiliations

  • Akhlaq A. Farooqui
    • 1
  • Lloyd A. Horrocks
    • 1
  1. 1.Department of Physiological ChemistryThe Ohio State UniversityColumbus

Personalised recommendations