Skip to main content
SpringerLink
Log in

Mucopolysaccharidoses and Oligosaccharidoses

  • Chapter
Inborn Metabolic Diseases

Abstract

Genetic defects of enzymes that are involved in the intralysosomal degradation of mucopolysaccharides (Fig. 36.1) and oligosaccharides lead to chronic and progressive storage disorders that share many clinical features varying from facial dysmorphism, bone and joint dysplasias, corneal clouding, hepatosplenomegaly, dwarfism, neurological abnormalities, mental regression and a reduced life span to an almost normal phenotype and life expectancy. Mucopolysaccharidoses (MPS) and oligosaccharidoses are transmitted in an autosomal-recessive manner, except for the X-linked MPS-II. Diagnosis of these lysosomal storage disorders can be made by enzyme assays in serum, leukocytes or fibroblasts. Partially degraded mucopolysaccharides and oligosaccharide fragments are excreted in the urine. Prenatal diagnosis is possible. As yet, treatment is mostly supportive. In some cases (especially in MPS-I), bone-marrow transplantation may improve the clinical course, but the value of this procedure is limited by the high risk and uncertain long-term neurological outcome. In the future, recombinant enzymes produced by genetically engineered cell lines may be available for MPS patients, at least for those in whom the central nervous system is not involved. Other therapeutic strategies, such as gene transfer into hematopoietic cells, are under consideration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Froissart R, Maire I, Millat G et al. (1998) Identification of iduronate sulfatase gene alterations in 7o unrelated Hunter patients. Clin Genet 53:362–368

    Article  PubMed  CAS  Google Scholar 

  2. Gourrier E, Thomas MP, Munnich A et al. (1997) 13-Mannosidose: une nouvelle observation. Arch Pediatr 4: 147–151

    Article  PubMed  CAS  Google Scholar 

  3. Cragg H, Williamson M, Young E et al. (1997) Fucosidosis: genetic and biochemical analysis of eight cases. J Med Genet 34: 105–110

    Article  PubMed  CAS  Google Scholar 

  4. Sewell AC, Poets CF, Degen I, Stoss H, Pontz BF (1996) The spectrum of free neuraminic acid storage disease in childhood: clinical, morphological and biochemical observations in three non-Finnish patients. Am J Med Genet 63: 203–208

    Article  PubMed  CAS  Google Scholar 

  5. Van Diggelen OP, Schindler D, Kleijer WJ et al. (1987) Lysosomal a-N-acetylgalactosaminidase deficiency: a new inherited metabolic disorder. Lancet 2: 804

    Article  PubMed  Google Scholar 

  6. Keulemans JL, Reuser AJ, Kroos MA et al. (1996) Human aN-acetylgalactosaminidase (a-NAGA) deficiency: new mutations and the paradox between genotype and phenotype. J Med Genet 33:458–464

    Article  PubMed  CAS  Google Scholar 

  7. Beck M, Barone R, Hoffmann R et al. (1995) Inter-and intrafamilial variability in mucolipidosis II (I-cell disease). Clin Genet 47:91–199

    Google Scholar 

  8. van der Spoel A, Bonten E, Azzo A (1998) Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A. EMBO J 17:1588–1597

    Article  PubMed  Google Scholar 

  9. Sewell AC, Gehler J, Spranger J (1979) Comprehensive urinary screening for inborn errors of complex carbohydrate metabolism. Klin Wochenschr 57:581–585

    Article  PubMed  CAS  Google Scholar 

  10. Renlund M (1984) Clinical and laboratory diagnosis of Salla disease in infancy and childhood. J Pediatr 104: 232–236

    Article  PubMed  CAS  Google Scholar 

  11. Thompson JN, Nowakowski RW (1991) Enzymatic diagnosis of selected mucopolysacharidoses. In: Hommes FA (ed) Techniques in diagnostic human biochemical genetics. Wiley-Liss, New York, pp 567–586

    Google Scholar 

  12. Colville GA, Watters JP, Yule W, Bax M (1996) Sleep problems in children with Sanfilippo syndrome. Dev Med Child Neurol 38:538–544

    Article  PubMed  CAS  Google Scholar 

  13. Hoogerbrugge PM, Brouwer OF, Bordigoni P et al. (1995) Allogeneic bone marrow transplantation for lysosomal storage diseases. Lancet 345: 1398–1402

    Article  PubMed  CAS  Google Scholar 

  14. Crawley AC, Niedzielski KH, Isaac EL et al. (1997) Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI. J Clin Invest 99: 651–662

    Article  PubMed  CAS  Google Scholar 

  15. Kakkis E, Muenzer J, Tiller G et al. (1998) Recombinant a-Liduronidase replacement therapy in mucopolysaccharidosis I: results of a human clinical trial. Annual meeting of the Society for Human Genetics, Denver, Oct 1998, abstract 128

    Google Scholar 

  16. Fillat C, Simonaro CM, Yeyati PL et al. (1996) Arylsulfatase B activities and glycosaminoglycan levels in retrovirally transduced mucopolysaccharidosis type VI cells. Prospects for gene therapy. J Clin Invest 98: 497–502

    Article  PubMed  CAS  Google Scholar 

  17. Fairbairn LJ, Lashford LS, Spooncer E et al. (1996) Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow. Proc Natl Acad Sci USA 93:2025–2030

    Google Scholar 

  18. Bielicki J, Hopwood JJ, Anson DS (1996) Correction of Sanfilippo A skin fibroblasts by retroviral vector-mediated gene transfer. Hum Gene Ther 7: 965–1970

    Article  Google Scholar 

  19. Ohashi T, Watabe K, Uehara K et al. (1997) Adenovirusmediated gene transfer and expression of human ß-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice. Proc Natl Acad Sci USA 94: 1287–1292

    Article  PubMed  CAS  Google Scholar 

  20. Gal A, Beck M, Sewell AC et al. (1992) Gene diagnosis and carrier detection in Hunter syndrome by the iduronate2-sulphatase cDNA probe. J Inherit Metab Dis 15: 342–346

    Article  PubMed  CAS  Google Scholar 

  21. Wenger DA, Williams C (1991) Screening for lysosomal disorders. In: Hommes FA (ed) Techniques in diagnostic human biochemical genetics. Wiley-Liss, New York, pp 587–617

    Google Scholar 

  22. Nelson J (1997) Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet 101:355–358

    Google Scholar 

  23. Stirling JL, Robinson D, Fensom AH, Benson PF, Baker JE (1978) Fluorimetric assay for prenatal detection of Hurler and Scheie homozygotes or heterozygotes (letter). Lancet 1: 147

    Article  PubMed  CAS  Google Scholar 

  24. Hopwood JJ (1979) alpha-L-iduronidase, beta-D-glucuronidase, and 2-sulfo-L-iduronate-2-sulfatase: preparation and characterization of radioactive substrates from heparin. Carbohydr Res 69:203–216

    Google Scholar 

  25. Karpova EA, Voznyi Ya V, Keulemans JL et al. (1996) A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type A ( MPS-IIIA ). J Inherit Metab Dis 19: 278–285

    Article  PubMed  CAS  Google Scholar 

  26. Marsh J, Fensom AH (1985) 4-Methylumbelliferyl cc-Nacetylglucosaminidase activity for diagnosis of Sanfilippo B disease. Clin Genet 27: 258–262

    Article  PubMed  CAS  Google Scholar 

  27. He W, Voznyi Ya V, Huijmans JG et al. (1994) Prenatal diagnosis of Sanfilippo disease type C using a simple fluorometric enzyme assay. Prenat Diagn 14: 17–22

    Google Scholar 

  28. He W, Voznyi Ya V, Boer AM, Kleijer WJ, van Diggelen OP (1993) A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type D (MPS-IIID). J Inherit Metab Dis 16:935–941

    Article  PubMed  CAS  Google Scholar 

  29. Yuen M, Fensom AH (1985) Diagnosis of classical Morquio’s disease: N-acetylgalactosamine 6-sulphate sulphatase activity in cultured fibroblasts, leukocytes, amniotic cells and chorionic villi. J Inherit Metab Dis 8: 80–86

    Article  PubMed  CAS  Google Scholar 

  30. Wenger DA, Sattler M, Clark C, Wharton C (1976) I-cell disease: activities of lysosomal enzymes toward natural and synthetic substrates. Life Sci 19: 413–420

    Article  PubMed  CAS  Google Scholar 

  31. Baum H, Dodgson KS, Spencer B (1959) The assay of arylsulfatase A and B in human urine. Clin Chim Acta 4:453–455

    Article  PubMed  CAS  Google Scholar 

  32. Glaser JH, Sly WS (1973) Beta-glucuronidase deficiency mucopolysaccharidosis: methods for enzymatic diagnosis. J Lab Clin Med 82:969–977

    PubMed  CAS  Google Scholar 

  33. Panday RS, van Diggelen OP, Kleijer WJ, Niermeijer MF (1984) ß-Mannosidase in human leukocytes and fibroblasts. J Inherit Metab Dis 7: 155–156

    Article  PubMed  CAS  Google Scholar 

  34. Beck M, Scheuring E, Voelter HU, Brandt J, Harzer K (1996) Neuraminidase assay in cultured human fibroblasts: in situ versus in vitro procedures. Clin Chim Acta 251: 163–171

    Article  PubMed  CAS  Google Scholar 

  35. Voznyi Ya V, Keulemans JL, Kleijer WJ et al. (1993) Applications of a new fluorimetric enzyme assay for the diagnosis of aspartylglucosaminuria. J Inherit Metab Dis 16: 929–934

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. M. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Veldweg 87, 8051 NP, Hattem, The Netherlands

    John Fernandes (Professor Emeritus of Pediatrics) (Professor Emeritus of Pediatrics)

  2. Hospital Necker-Enfants Malades, 149 Rue de Sevres, 75743, Paris Cedex 15, France

    Jean-Marie Saudubray

  3. Institute of Cellular Pathology, Université Catholique de Louvain, Avenue Hippocrate 75, 1200, Brussels, Belgium

    Georges Van den Berghe (Christian de Duve) (Christian de Duve)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Beck, M. (2000). Mucopolysaccharidoses and Oligosaccharidoses. In: Fernandes, J., Saudubray, JM., Van den Berghe, G. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04285-4_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04285-4_36

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04287-8

  • Online ISBN: 978-3-662-04285-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation