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The mucopolysaccharidoses: a success of molecular medicine

Published online by Cambridge University Press:  18 January 2008

Lorne A. Clarke
Affiliation:
University of British Columbia, Child and Family Research Institute, Department of Medical Genetics, 4500 Oak Street, Room C234, Vancouver, British Columbia, Canada, V6H 3N1. Tel: +1 604 875 3526; Fax: +1 604 875 2376; E-mail: [email protected]

Abstract

The mucopolysaccharidoses represent a devastating group of lysosomal storage diseases affecting approximately 1 in 25 000 individuals. Advances in biochemistry and genetics over the past 25 years have resulted in the identification of the key hydrolases underlying the mucopolysaccharidoses, with subsequent isolation and characterisation of the genes involved. Ultimately these advances have led to the recent development of specific treatment regimens for some of the mucopolysaccharidoses, in the form of direct enzyme replacement. Direct replacement of the defective gene product has been attempted for very few genetic disorders, and thus the experience gained in the lysosomal storage diseases by the development, evaluation and integration of treatment regimens into healthcare is instructive for other rare genetic disorders. This review focuses on the pathophysiology of the mucopolysaccharidoses and highlights the complex biochemical and physiological perturbations that underlie the disease phenotype.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Key patient support group websites:

Walkley, S.U. (2007) Pathogenic mechanisms in lysosomal disease: a reappraisal of the role of the lysosome. Acta Paediatr Suppl 96, 26-32CrossRefGoogle ScholarPubMed
Ponder, K.P. and Haskins, M.E. (2007) Gene therapy for mucopolysaccharidosis. Expert Opin Biol Ther 7, 1333-1345CrossRefGoogle ScholarPubMed
Sillence, D.J. (2007) New insights into glycosphingolipid functions—storage, lipid rafts, and translocators. Int Rev Cytol 262, 151-189CrossRefGoogle ScholarPubMed
Simons, K. and Gruenberg, J. (2000) Jamming the endosomal system: lipid rafts and lysosomal storage diseases. Trends Cell Biol 10, 459-462CrossRefGoogle ScholarPubMed
http://www.goldinfo.org: (Global Organisation for Lysosomal Diseases)Google Scholar
http://www.rarediseases.org (National Organization for Rare Diseases)Google Scholar
Walkley, S.U. (2007) Pathogenic mechanisms in lysosomal disease: a reappraisal of the role of the lysosome. Acta Paediatr Suppl 96, 26-32CrossRefGoogle ScholarPubMed
Ponder, K.P. and Haskins, M.E. (2007) Gene therapy for mucopolysaccharidosis. Expert Opin Biol Ther 7, 1333-1345CrossRefGoogle ScholarPubMed
Sillence, D.J. (2007) New insights into glycosphingolipid functions—storage, lipid rafts, and translocators. Int Rev Cytol 262, 151-189CrossRefGoogle ScholarPubMed
Simons, K. and Gruenberg, J. (2000) Jamming the endosomal system: lipid rafts and lysosomal storage diseases. Trends Cell Biol 10, 459-462CrossRefGoogle ScholarPubMed
http://www.goldinfo.org: (Global Organisation for Lysosomal Diseases)Google Scholar
http://www.rarediseases.org (National Organization for Rare Diseases)Google Scholar