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. 1976 Feb;73(2):630–637. doi: 10.1073/pnas.73.2.630

The mucopolysaccharidoses (a review).

A Dorfman, R Matalon
PMCID: PMC335965  PMID: 813230

Abstract

The mucopolysaccharidoses are a group of genetic diseases characterized by storage of incompletely degraded glycosaminoglycans. Such storage causes marked distortion of many tissues with consequent severe somatic changes and mental retardation. Storage of glycosaminoglycans results from markedly diminished activity of specific hydrolases requisite for the normal degradation of glycosaminoglycans. The specific enzymic defects have been identified in nine different diseases. In some cases evidence has been obtained indicating the existence of additional allelic diseases based on the same enzyme. The knowledge obtained from these studies has made prenatal diagnosis possible and has led to the possibility that therapy may be undertaken utilizing enzyme replacement.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arbogast B., Hopwood J. J., Dorfman A. Absence of hyaluronidase in cultured human skin fibroblasts. Biochem Biophys Res Commun. 1975 Nov 3;67(1):376–382. doi: 10.1016/0006-291x(75)90326-5. [DOI] [PubMed] [Google Scholar]
  2. Austin J. H. Studies in metachromatic leukodystrophy. XII. Multiple sulfatase deficiency. Arch Neurol. 1973 Apr;28(4):258–264. doi: 10.1001/archneur.1973.00490220066010. [DOI] [PubMed] [Google Scholar]
  3. BARKER S. A., STACEY M. The pathology and chemistry of a case of gargoylism. Appendix. Chemical analysis of tissue polysaccharides. J Clin Pathol. 1956 Nov;9(4):314–315. [PubMed] [Google Scholar]
  4. BRANTE G. Gargoylism; a mucopolysaccharidosis. Scand J Clin Lab Invest. 1952;4(1):43–46. doi: 10.3109/00365515209060631. [DOI] [PubMed] [Google Scholar]
  5. Bach G., Eisenberg F., Jr, Cantz M., Neufeld E. F. The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2134–2138. doi: 10.1073/pnas.70.7.2134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bach G., Friedman R., Weissmann B., Neufeld E. F. The defect in the Hurler and Scheie syndromes: deficiency of -L-iduronidase. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2048–2051. doi: 10.1073/pnas.69.8.2048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barton R. W., Neufeld E. F. The Hurler corrective factor. Purification and some properties. J Biol Chem. 1971 Dec 25;246(24):7773–7779. [PubMed] [Google Scholar]
  8. Beaudet A. L., DiFerrante N. M., Ferry G. D., Nichols B. L., Jr, Mullins C. E. Variation in the phenotypic expression of beta-glucuronidase deficiency. J Pediatr. 1975 Mar;86(3):388–394. doi: 10.1016/s0022-3476(75)80968-1. [DOI] [PubMed] [Google Scholar]
  9. Beratis N. G., Turner B. M., Weiss R., Hirschhorn K. Arylsulfatase B deficiency in Maroteaux-Lamy syndrome: Cellular studies and carrier identification. Pediatr Res. 1975 May;9(5):475–480. doi: 10.1203/00006450-197505000-00003. [DOI] [PubMed] [Google Scholar]
  10. Brown D. H. TISSUE STORAGE OF MUCOPOLYSACCHARIDES IN HURLER-PFAUNDLER'S DISEASE. Proc Natl Acad Sci U S A. 1957 Sep 15;43(9):783–790. doi: 10.1073/pnas.43.9.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cantz M., Chrambach A., Neufeld E. F. Characterization of the factor deficient in the Hunter syndrome by polyacrylamide gel electrophoresis. Biochem Biophys Res Commun. 1970 Jun 5;39(5):936–942. doi: 10.1016/0006-291x(70)90414-6. [DOI] [PubMed] [Google Scholar]
  12. Cantz M., Kresse H. Sandhoff disease: defective glycosaminoglycan catabolism in cultured fibroblasts and its correction by beta-N-acetylhexosaminidase. Eur J Biochem. 1974 Sep 16;47(3):581–590. doi: 10.1111/j.1432-1033.1974.tb03729.x. [DOI] [PubMed] [Google Scholar]
  13. Cashman D. C., Laryea J. U., Weissmann B. The hyaluronidase of rat skin. Arch Biochem Biophys. 1969 Dec;135(1):387–395. doi: 10.1016/0003-9861(69)90554-2. [DOI] [PubMed] [Google Scholar]
  14. Cifonelli J. A., King J. The distribution of sulfated uronic acid and hexosamine residues in heparin and heparan sulfate. Connect Tissue Res. 1975;3(1):97–104. doi: 10.3109/03008207509152346. [DOI] [PubMed] [Google Scholar]
  15. Danes B. S., Bearn A. G. Hurler's syndrome: demonstration of an inherited disorder of connective tissue in cell culture. Science. 1965 Aug 27;149(3687):987–989. doi: 10.1126/science.149.3687.987. [DOI] [PubMed] [Google Scholar]
  16. Di Ferrante N., Hyman B. H., Klish W., Donnelly P. V., Nichols B. L., Dutton R. V. Mucopolysaccharidosis VI (Maroteaux-Lamy disease). Clinical and biochemical study of a mild variant case. Johns Hopkins Med J. 1974 Jul;135(1):42–54. [PubMed] [Google Scholar]
  17. Dorfman A., Lorincz A. E. OCCURRENCE OF URINARY ACID MUCOPOLYSACCHARIDES IN THE HURLER SYNDROME. Proc Natl Acad Sci U S A. 1957 Jun 15;43(6):443–446. doi: 10.1073/pnas.43.6.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Eto Y., Wiesmann U. N., Carson J. H., Herschkowitz N. N. Multiple sulfatase deficiencies in cultured skin fibroblasts. Occurrence in patients with a variant form of metachromatic leukodystrophy. Arch Neurol. 1974 Feb;30(2):153–156. doi: 10.1001/archneur.1974.00490320041005. [DOI] [PubMed] [Google Scholar]
  19. Fluharty A. L., Stevens R. L., Sanders D. L., Kihara H. Arylsulfatase B deficiency in Maroteaux-Lamy syndrome cultured fibroblasts. Biochem Biophys Res Commun. 1974 Jul 24;59(2):455–461. doi: 10.1016/s0006-291x(74)80001-x. [DOI] [PubMed] [Google Scholar]
  20. Fratantoni J. C., Hall C. W., Neufeld E. F. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science. 1968 Nov 1;162(3853):570–572. doi: 10.1126/science.162.3853.570. [DOI] [PubMed] [Google Scholar]
  21. Fratantoni J. C., Hall C. W., Neufeld E. F. The defect in Hurler and Hunter syndromes. II. Deficiency of specific factors involved in mucopolysaccharide degradation. Proc Natl Acad Sci U S A. 1969 Sep;64(1):360–366. doi: 10.1073/pnas.64.1.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fratantoni J. C., Hall C. W., Neufeld E. F. The defect in Hurler's and Hunter's syndromes: faulty degradation of mucopolysaccharide. Proc Natl Acad Sci U S A. 1968 Jun;60(2):699–706. doi: 10.1073/pnas.60.2.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Friedman R. B., Weissmann B. The phenyl - and -L-idopyranosiduronic acids and some other aryl glycopyranosiduronic acids. Carbohydr Res. 1972 Sep;24(1):123–131. doi: 10.1016/s0008-6215(00)82265-x. [DOI] [PubMed] [Google Scholar]
  24. Gehler J., Cantz M., Tolksdorf M., Spranger J., Gilbert E., Drube H. Mucopolysaccharidosis. VII. Beta-glucuronidase deficiency. Humangenetik. 1974 Jul 15;23(2):149–158. doi: 10.1007/BF00282212. [DOI] [PubMed] [Google Scholar]
  25. Hall C. W., Cantz M., Neufeld E. F. A -glucuronidase deficiency mucopolysaccharidosis: studies in cultured fibroblasts. Arch Biochem Biophys. 1973 Mar;155(1):32–38. doi: 10.1016/s0003-9861(73)80006-2. [DOI] [PubMed] [Google Scholar]
  26. Hickman S., Neufeld E. F. A hypothesis for I-cell disease: defective hydrolases that do not enter lysosomes. Biochem Biophys Res Commun. 1972 Nov 15;49(4):992–999. doi: 10.1016/0006-291x(72)90310-5. [DOI] [PubMed] [Google Scholar]
  27. Hickman S., Shapiro L. J., Neufeld E. F. A recognition marker required for uptake of a lysosomal enzyme by cultured fibroblasts. Biochem Biophys Res Commun. 1974 Mar 15;57(1):55–61. doi: 10.1016/s0006-291x(74)80356-6. [DOI] [PubMed] [Google Scholar]
  28. Hunter C. A Rare Disease in Two Brothers. Proc R Soc Med. 1917;10(SECT):104–116. [PMC free article] [PubMed] [Google Scholar]
  29. Hutterer F. Degradation of mucopolysaccharides by hepatic lysosomes. Biochim Biophys Acta. 1966 Feb 28;115(2):312–319. doi: 10.1016/0304-4165(66)90430-2. [DOI] [PubMed] [Google Scholar]
  30. KROOTH R. S., WEINBERG A. N. Properties of galactosemic cells in culture. Biochem Biophys Res Commun. 1960 Nov;3:518–524. doi: 10.1016/0006-291x(60)90167-4. [DOI] [PubMed] [Google Scholar]
  31. Kaplan D. Classification of the mucopolysaccharidoses based on the pattern of mucopolysacchariduria. Am J Med. 1969 Nov;47(5):721–729. doi: 10.1016/0002-9343(69)90166-1. [DOI] [PubMed] [Google Scholar]
  32. Kaplan D., McKusick V., Trebach S., Lazarus R. Keratosulfate-chondroitin sulfate peptide from normal urine and from urine of patients with Morquio syndrome (mucopolysaccharidosis IV). J Lab Clin Med. 1968 Jan;71(1):48–55. [PubMed] [Google Scholar]
  33. Knecht J., Cifonelli J. A., Dorfman A. Structural studies on heparitin sulfate of normal and Hurler tissues. J Biol Chem. 1967 Oct 25;242(20):4652–4661. [PubMed] [Google Scholar]
  34. Kresse H. Mucopolysaccharidosis 3 A (Sanfilippo A disease): deficiency of a heparin sulfamidase in skin fibroblasts and leucocytes. Biochem Biophys Res Commun. 1973 Oct 1;54(3):1111–1118. doi: 10.1016/0006-291x(73)90807-3. [DOI] [PubMed] [Google Scholar]
  35. Kresse H., Neufeld E. F. The Sanfilippo A corrective factor. Purification and mode of action. J Biol Chem. 1972 Apr 10;247(7):2164–2170. [PubMed] [Google Scholar]
  36. Kresse H., Wiesmann U., Cantz M., Hall C. W., Neufeld E. F. Biochemical heterogeneity of the Sanfilippo syndrome: preliminary characterization of two deficient factors. Biochem Biophys Res Commun. 1971 Mar 5;42(5):892–898. doi: 10.1016/0006-291x(71)90514-6. [DOI] [PubMed] [Google Scholar]
  37. Lichtenstein J. R., Bilbrey G. L., McKusick V. A. Clinical and probable genetic heterogeneity within mucopolysaccharidosis. II. Report of a family with a mild form. Johns Hopkins Med J. 1972 Dec;131(6):425–435. [PubMed] [Google Scholar]
  38. Lim T. W., Leder I. G., Bach G., Neufeld E. F. An assay for iduronate sulfatase (Hunter corrective factor). Carbohydr Res. 1974 Oct;37(1):103–109. doi: 10.1016/s0008-6215(00)87067-6. [DOI] [PubMed] [Google Scholar]
  39. Lindahl U., Axelsson O. Identification of iduronic acid as the major sulfated uronic acid of heparin. J Biol Chem. 1971 Jan 10;246(1):74–82. [PubMed] [Google Scholar]
  40. MAROTEAUX P., LEVEQUE B., MARIE J., LAMY M. UNE NOUVELLE DYSOSTOSE AVEC 'ELIMINATION URINAIRE DE CHONDROITINE-SULFATE B. Presse Med. 1963 Sep 25;71:1849–1852. [PubMed] [Google Scholar]
  41. MEYER K., GRUMBACH M. M., LINKER A., HOFFMAN P. Excretion of sulfated mucopolysaccharides in gargoylism (Hurler's syndrome). Proc Soc Exp Biol Med. 1958 Feb;97(2):275–279. doi: 10.3181/00379727-97-23714. [DOI] [PubMed] [Google Scholar]
  42. Malmström A., Fransson L. A. Structure of pig skin dermatan sulfate. 2. Demonstration of sulfated iduronic acid residues. Eur J Biochem. 1971 Feb 1;18(3):431–435. doi: 10.1111/j.1432-1033.1971.tb01260.x. [DOI] [PubMed] [Google Scholar]
  43. Matalon R., Arbogast B., Dorfman A. Deficiency of chondroitin sulfate N-acetylgalactosamine 4-sulfate sulfatase in Maroteaux-Lamy syndrome. Biochem Biophys Res Commun. 1974 Dec 23;61(4):1450–1457. doi: 10.1016/s0006-291x(74)80446-8. [DOI] [PubMed] [Google Scholar]
  44. Matalon R., Arbogast B., Justice P., Brandt I. K., Dorfman A. Morquio's syndrome: deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase. Biochem Biophys Res Commun. 1974 Nov 27;61(2):759–765. doi: 10.1016/0006-291x(74)91022-5. [DOI] [PubMed] [Google Scholar]
  45. Matalon R., Cifonelli J. A., Dorfman A. L-iduronidase in cultured human fibroblasts and liver. Biochem Biophys Res Commun. 1971 Jan 22;42(2):340–345. doi: 10.1016/0006-291x(71)90108-2. [DOI] [PubMed] [Google Scholar]
  46. Matalon R., Cifonelli J. A., Dorfman A. L-iduronidase in cultured human fibroblasts and liver. Biochem Biophys Res Commun. 1971 Jan 22;42(2):340–345. doi: 10.1016/0006-291x(71)90108-2. [DOI] [PubMed] [Google Scholar]
  47. Matalon R., Dorfman A. Sanfilippo A syndrome: sulfamidase deficiency in cultured skin fibroblasts and liver. J Clin Invest. 1974 Oct;54(4):907–912. doi: 10.1172/JCI107830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. McKusick V. A., Howell R. R., Hussels I. E., Neufeld E. F., Stevenson R. E. Allelism, non-allelism, and genetic compounds among the mucopolysaccharidoses. Lancet. 1972 May 6;1(7758):993–996. doi: 10.1016/s0140-6736(72)91159-2. [DOI] [PubMed] [Google Scholar]
  49. McKusick V. A., Kaplan D., Wise D., Hanley W. B., Suddarth S. B., Sevick M. E., Maumanee A. E. The genetic mucopolysaccharidoses. Medicine (Baltimore) 1965 Nov;44(6):445–483. doi: 10.1097/00005792-196511000-00001. [DOI] [PubMed] [Google Scholar]
  50. Milunsky A., Neufeld E. F. The Hunter syndrome in a 46 XX girl. N Engl J Med. 1973 Jan 11;288(2):106–107. doi: 10.1056/nejm197301112880220. [DOI] [PubMed] [Google Scholar]
  51. Neufeld E. F., Cantz M. J. Corrective factors for inborn errors of mucopolysaccharide metabolism. Ann N Y Acad Sci. 1971 Jul 6;179:580–587. doi: 10.1111/j.1749-6632.1971.tb46934.x. [DOI] [PubMed] [Google Scholar]
  52. O'Brien J. F., Cantz M., Spranger J. Maroteaux-Lamy disease (mucopolysaccharidosis VI), subtype A: deficiency of a N-acetylgalactosamine-4-sulfatase. Biochem Biophys Res Commun. 1974 Oct 8;60(3):1170–1177. doi: 10.1016/0006-291x(74)90435-5. [DOI] [PubMed] [Google Scholar]
  53. O'Brien J. S. Sanfilippo syndrome: profound deficiency of alpha-acetylglucosaminidase activity in organs and skin fibroblasts from type-B patients. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1720–1722. doi: 10.1073/pnas.69.7.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ogren S., Lindahl U. Cleavage of macromolecular heparin by an enzyme from mouse mastocytoma. J Biol Chem. 1975 Apr 10;250(7):2690–2697. [PubMed] [Google Scholar]
  55. PAULING L., ITANO H. A. Sickle cell anemia a molecular disease. Science. 1949 Nov 25;110(2865):543–548. doi: 10.1126/science.110.2865.543. [DOI] [PubMed] [Google Scholar]
  56. PEDRINI V., LENNZI L., ZAMBOTTI V. Isolation and identification of keratosulphate in urine of patients affected by Morquio-Ullrich disease. Proc Soc Exp Biol Med. 1962 Aug-Sep;110:847–849. doi: 10.3181/00379727-110-27668. [DOI] [PubMed] [Google Scholar]
  57. Punnett H. H. Hunter syndrome in girl. N Engl J Med. 1973 Apr 19;288(16):856–856. doi: 10.1056/nejm197304192881623. [DOI] [PubMed] [Google Scholar]
  58. SCHEIE H. G., HAMBRICK G. W., Jr, BARNESS L. A. A newly recognized forme fruste of Hurler's disease (gargoylism). Am J Ophthalmol. 1962 May;53:753–769. [PubMed] [Google Scholar]
  59. Schafer I. A., Sullivan J. C., Svejcar J., Kofoed J., Robertson W. van B. Vitamin C-induced increase of dermatan sulfate in cultured Hurler's fibroblasts. Science. 1966 Aug 26;153(3739):1008–1010. doi: 10.1126/science.153.3739.1008. [DOI] [PubMed] [Google Scholar]
  60. Shapira E., DeGregorio R. R., Matalon R., Nadler H. L. Reduced arylsulfatase B activity of the mutant enzyme protein in Maroteaux-Lamy syndrome. Biochem Biophys Res Commun. 1975 Jan 20;62(2):448–455. doi: 10.1016/s0006-291x(75)80159-8. [DOI] [PubMed] [Google Scholar]
  61. Sjöberg I., Fransson L. A., Matalon R., Dorfman A. Hunter's syndrome: a deficiency of L-idurono-sulfate sulfatase. Biochem Biophys Res Commun. 1973 Oct 1;54(3):1125–1132. doi: 10.1016/0006-291x(73)90809-7. [DOI] [PubMed] [Google Scholar]
  62. Sly W. S., Quinton B. A., McAlister W. H., Rimoin D. L. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973 Feb;82(2):249–257. doi: 10.1016/s0022-3476(73)80162-3. [DOI] [PubMed] [Google Scholar]
  63. Spranger J. The systemic mucopolysaccharidoses. Ergeb Inn Med Kinderheilkd. 1972;32:165–265. doi: 10.1007/978-3-642-65300-1_4. [DOI] [PubMed] [Google Scholar]
  64. Tanaka H., Suzuki K. Lactosylceramide beta-galactosidase in human sphingolipidoses. Evidence for two genetically distinct enzymes. J Biol Chem. 1975 Mar 25;250(6):2324–2332. [PubMed] [Google Scholar]
  65. Tsay G. C., Dawson G. Structure of the "keratosulfate-like" material in liver from a patient with G M1 -gangliosidosis ( -D-galactosidase deficiency). Biochem Biophys Res Commun. 1973 Jun 8;52(3):759–766. doi: 10.1016/0006-291x(73)91002-4. [DOI] [PubMed] [Google Scholar]
  66. VANHOOF F., HERS H. G. L'ULTRASTRUCTURE LES CELLULES H'EPATIQUES DANS LA MALADIE DE HUERLER (GARGOYLISME) C R Hebd Seances Acad Sci. 1964 Aug 3;259:1281–1283. [PubMed] [Google Scholar]
  67. Weissmann B., Santiago R. -L-iduronidase in lysosomal extracts. Biochem Biophys Res Commun. 1972 Feb 16;46(3):1430–1433. doi: 10.1016/s0006-291x(72)80136-0. [DOI] [PubMed] [Google Scholar]
  68. Wiesmann U., Neufeld E. F. Scheie and Hurler syndromes: apparent identity of the biochemical defect. Science. 1970 Jul 3;169(3940):72–74. doi: 10.1126/science.169.3940.72. [DOI] [PubMed] [Google Scholar]
  69. von Figura K., Kresse H. The sanfilippo B corrective factor: a N-acetyl-alpha-D-glucosamindiase. Biochem Biophys Res Commun. 1972 Jul 25;48(2):262–269. doi: 10.1016/s0006-291x(72)80044-5. [DOI] [PubMed] [Google Scholar]

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