Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1980 Nov;77(11):6822–6826. doi: 10.1073/pnas.77.11.6822

Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

H Kresse, E Paschke, K von Figura, W Gilberg, W Fuchs
PMCID: PMC350382  PMID: 6450420

Abstract

Skin fibroblasts from two patients who had symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated excessive amounts of heparan sulfate and were unable to release sulfate from N-acetylglucosamine-6-sulfate linkages in heparan sulfate-derived oligosaccharides. Keratan sulfate-derived oligosaccharides bearing the same residue at the nonreducing end and p-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside were degraded normally. Kinetic differences between th sulfatase activities of normal fibroblasts were found. These observations suggest that N-acetylglucosamine-6-sulfate sulfatase activities degrading heparan sulfate and keratan sulfate, respectively, can be distinguished. It is the activity directed toward heparan sulfate that is deficient in these patients; we propose that this deficiency causes Sanfilippo disease type D.

Full text

PDF
6822

Selected References

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

  1. BAUM H., DODGSON K. S., SPENCER B. The assay of arylsulphatases A and B in human urine. Clin Chim Acta. 1959 May;4(3):453–455. doi: 10.1016/0009-8981(59)90119-6. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Basner R., Kresse H., von Figura K. N-Acetylglucosamine-6-sulfate sulfatase from human urine. J Biol Chem. 1979 Feb 25;254(4):1151–1158. [PubMed] [Google Scholar]
  5. Basner R., von Figura K., Glössl J., Klein U., Kresse H., Mlekusch W. Multiple deficiency of mucopolysaccharide sulfatases in mucosulfatidosis. Pediatr Res. 1979 Dec;13(12):1316–1318. doi: 10.1203/00006450-197912000-00002. [DOI] [PubMed] [Google Scholar]
  6. Di Ferrante N., Ginsberg L. C., Donnelly P. V., Di Ferrante D. T., Caskey C. T. Deficiencies of glucosamine-6-sulfate or galactosamine-6-sulfate sulfatases are responsible for different mucopolysaccharidoses. Science. 1978 Jan 6;199(4324):79–81. doi: 10.1126/science.199.4324.79. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Gamse G., Fromme H. G., Kresse H. Metabolism of sulfated glycosaminoglycans in cultured endothelial cells and smooth muscle cells from bovine aorta. Biochim Biophys Acta. 1978 Dec 18;544(3):514–528. doi: 10.1016/0304-4165(78)90326-4. [DOI] [PubMed] [Google Scholar]
  9. Ginsberg L. C., Donnelly P. V., Di Ferrante D. T., Di Ferrante N., Caskey C. T. N-acetylglucosamine-6-sulfate sulfatase in man: deficiency of the enzyme in a new mucopolysaccharidosis. Pediatr Res. 1978 Jul;12(7):805–809. doi: 10.1203/00006450-197807000-00015. [DOI] [PubMed] [Google Scholar]
  10. Groebe H., Krins M., Schmidberger H., von Figura K., Harzer K., Kresse H., Paschke E., Sewell A., Ullrich K. Morquio syndrome (mucopolysaccharidosis IV B) associated with beta-galactosidase deficiency. Report of two cases. Am J Hum Genet. 1980 Mar;32(2):258–272. [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Hök M., Wasteson A., Oldberg A. A heparan sulfate-degrading endoglycosidase from rat liver tissue. Biochem Biophys Res Commun. 1975 Dec 15;67(4):1422–1428. doi: 10.1016/0006-291x(75)90185-0. [DOI] [PubMed] [Google Scholar]
  13. Ishihara K., Sobue M., Uemura D., Tsuji M., Nakanishi Y. N-Acetylgalactosamine 4,6-bissulfate in rat urine. I. Isolation, identification and chemical synthesis. Biochim Biophys Acta. 1976 Jul 21;437(2):416–430. doi: 10.1016/0304-4165(76)90011-8. [DOI] [PubMed] [Google Scholar]
  14. Klein U., Kresse H., von Figura K. Evidence for degradation of heparan sulfate by endoglycosidases: glucosamine and hexuronic acid are reducing terminals of intracellular heparan sulfate from human skin fibroblasts. Biochem Biophys Res Commun. 1976 Mar 8;69(1):158–166. doi: 10.1016/s0006-291x(76)80286-0. [DOI] [PubMed] [Google Scholar]
  15. Klein U., Kresse H., von Figura K. Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5185–5189. doi: 10.1073/pnas.75.10.5185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Kresse H., Von Figura K., Klein U. A new biochemical subtype of the Sanfilippo syndrome: characterization of the storage material in cultured fibroblasts of Sanfilippo C patients. Eur J Biochem. 1978 Dec;92(2):333–339. doi: 10.1111/j.1432-1033.1978.tb12752.x. [DOI] [PubMed] [Google Scholar]
  19. Lohmander S., Moskalewski S., Madsen K., Thyberg J., Friberg U. Influence of colchicine on the synthesis and secretion of proteoglycans and collagen by fetal guinea pig chondrocytes. Exp Cell Res. 1976 May;99(2):333–345. doi: 10.1016/0014-4827(76)90591-7. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Mega T., Matsushima Y. Affinity chromatography of glycosidases. II. Studies on specific and non-specific binding. J Biochem. 1977 Mar;81(3):571–578. doi: 10.1093/oxfordjournals.jbchem.a131492. [DOI] [PubMed] [Google Scholar]
  23. Nakazawa K., Suzuki S. Purification of Keratan Sulfate-endogalactosidase and its action on keratan sulfates of different origin. J Biol Chem. 1975 Feb 10;250(3):912–917. [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. 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]
  27. 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]
  28. Wasteson A., Hök M., Westermark B. Demonstration of a platelet enzyme, degrading heparan sulphate. FEBS Lett. 1976 Apr 15;64(1):218–221. doi: 10.1016/0014-5793(76)80287-6. [DOI] [PubMed] [Google Scholar]
  29. von Figura K. Human alpha-N-acetylglucosaminidase. 1. Purification and properties. Eur J Biochem. 1977 Nov 1;80(2):523–533. [PubMed] [Google Scholar]
  30. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES