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Mucopolysaccharidosis I

  • Lorne A. Clarke

Mucopolysaccharidosis type I (MPS I) has historically been considered to represent the prototypical generalized storage disease. As such, insights provided by clinical observations, therapeutic attempts, and the understanding of the molecular basis of disease pathophysiology of this disease, are likely to be applicable to most of the generalized lysosomal disorders. The detailed delineation of the natural history of this disorder has been particularly instructive. Deficiency of the lysosomal enzyme α-L-iduronidase (IDUA; EC 3.2.1.76) is the primary defect in MPS I. Interestingly, the initial clinical classification of the MPSs included a separate group of patients classified as MPS V (McKusick et al., 1965). It was not until the lysosomal enzyme iduronidase was discovered that it soon became known that MPS I (Hurler syndrome) and MPS V (Scheie syndrome) patients had the same primary metabolic defect (Wiesmann and Neufeld, 1970). The clinical distinctiveness of the two groups related to the fact that they represented opposite ends of a wide clinical disease spectrum. This concept of “disease spectrum” is now considered universal in the lysosomal storage disorders (LSDs). For most of the LSDs this disease spectrum is caused primarily by different mutations within the gene coding for the deficient hydrolase or transporter, that is, allelic heterogeneity. On the other hand, observations in Gaucher disease (Beutler et al., 2004; Zhao et al., 2003; Beutler 2001) and Fabry disease (Germain et al., 2002; Ashton-Prolla et al., 2000; Knol et al., 1999) indicate that significant clinical heterogeneity can be seen for patients that have identical mutations. These disorders indicate the likelihood of modifier genes that modulate the disease phenotype. Detailed understanding of the molecular basis of the LSDs will reveal important insights into the various mechanisms that underlie clinical heterogeneity. The genotype-phenotype observations for MPS I have been particularly instructive in this regard as will further insights into the identification of factors that modify the disease severity of other lysosomal disorders.

Keywords

Bone Marrow Transplantation Enzyme Replacement Therapy Fabry Disease Gauche Disease Dermatan Sulfate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alroy, J., Haskins, M., and Birk, D. E., 1999, Altered corneal stromal matrix organization is associated with mucopolysaccharidosis I, III and VI. Exp. Eye. Res. 68:523.CrossRefPubMedGoogle Scholar
  2. Ashton, L. J., Brooks, D. A., McCourt, P. A., Muller, V. J., Clements, P. R., and Hopwood, J. J., 1992, Immunoquantification and enzyme kinetics of alpha-Liduronidase in cultured fibroblasts from normal controls and mucopolysaccharidosis type I patients. Am. J. Hum. Gene. 50:787.Google Scholar
  3. Ashton-Prolla, P., Tong, B., Shabbeer, J., Astrin, K. H., Eng, C. M., and Desnick R. J., 2000, Fabry disease: Twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes. J. Investig. Med. 48:227.PubMedGoogle Scholar
  4. Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E.P., Winchester, B.G., 2001, Mutational analysis of 85 mucopolysaccharidosis type I families: Frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum. Genet. 109:503.CrossRefPubMedGoogle Scholar
  5. Benevides, G., Pimentel, E., Toyama, M., Novello, J. C., Marangoni, S., and Gomes, L., 2004, Biochemical and biomechanical analysis of tendons of caged and penned chickens. Connect Tissue Res. 45:206.CrossRefPubMedGoogle Scholar
  6. Bernfield, M., Götte, M., Park, P. W., Reizes, O., Marilyn, L. Fitzgerald, M. L., Lincecum, J., and Zako, M., 1999, Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68:729.CrossRefPubMedGoogle Scholar
  7. Beutler E., 2001, Discrepancies between genotype and phenotype in hematology: an important frontier. Blood. 98:2597.CrossRefPubMedGoogle Scholar
  8. Beutler, E., Beutler, L., and West, C., 2004, Mutations in the gene encoding cytosolic beta-glucosidase in Gaucher disease. J. Lab. Clin. Med. 144:65.CrossRefPubMedGoogle Scholar
  9. Braunlin, E. A., Rose, A. G., Hopwood, J. J., Candel, R. D., and Krivit, W., 2001, Coronary artery patency following long-term successful engraftment 14 years after bone marrow transplantation in the Hurler syndrome. Am. J. Cardiol. 88:1075.CrossRefPubMedGoogle Scholar
  10. Braunlin, E. A., Stauffer, N. R., Peters, C. H., Bass, J. L., Berry, J. M., Hopwood, J. J., and Krivit, W., 2003, Usefulness of bone marrow transplantation in the Hurler syndrome. Am. J. Cardiol., 92:882.CrossRefPubMedGoogle Scholar
  11. Brooks, D. A., Fabrega, S., Hein, L. K., Parkinson, E. J., Durand, P., Yogalingam, G., Matte, U., Giugliani, R., Dasvarma, A., Eslahpazire, J., Henrissat, B., Mornon, J. P., Hopwood, J. J., and Lehn, P., 2001, Glycosidase active site mutations in human alpha-L-iduronidase. Glycobiology. 11:741.CrossRefPubMedGoogle Scholar
  12. Bunge, S., Clements, P. R., Byers, S., Kleijer, W. J., Brooks, D.A., and Hopwood, J. J., 1998, Genotype-phenotype  correlations in MPS I using  enzyme  kinetics, immunoquantification and in vitro turnover studies. Bioch. Biophy. Acta. 1407:249.Google Scholar
  13. Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., and Gal, A., 1995, Mucopolysaccharidosis type I: Identification of 13 novel mutations of the α-L-iduronidase gene. Hum. Mutat. 6:91.CrossRefPubMedGoogle Scholar
  14. Clarke, L. A., Nelson, P. V., Warrington, C. L., Morris, C. P., Hopwood, J. J., and Scott, H. S., 1994, Mutation analysis of 19 North American mucopolysaccharidosis type I patients: Identification of two additional frequent mutations. Hum. Mutat. 3:275.CrossRefPubMedGoogle Scholar
  15. Cleary, M. A., and Wraith, J. E., 1995, The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). Acta. Paediatr. 84:337.CrossRefPubMedGoogle Scholar
  16. Fan, J.-Q., 2003, A contradictory treatment for lysosomal storage disorders: Inhibitors enhance mutant enzyme activity. Trends Pharm. Sci. 24:355.Google Scholar
  17. Fan, J. Q., Ishii, S., Asano, N., and Suzuki, 1999, Accelerated transport and maturation of lysosomal a-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat. Med. 5:112.CrossRefPubMedGoogle Scholar
  18. Fuller, M., Brooks, D. A., Evangelista, M., Hein, L. K., Hopwood, J. J., and Meikle, P. J., 2005, Prediction of neuropathology in mucopolysaccharidosis I patients. Mol. Genet. Metab. 84:18.CrossRefPubMedGoogle Scholar
  19. Gassas, A., Sung, L., Doyle, J. J., Clarke, J. T., and Saunders, E. F., 2003, Life-threatening pulmonary hemorrhages post bone marrow transplantation in Hurler syndrome. Report of three cases and review of the literature. Bone Marrow Transplant. 32:213.CrossRefPubMedGoogle Scholar
  20. Germain, D. P., Shabbeer, J., Cotigny, S., Desnick, R. J., 2002, Fabry disease: twenty novel alpha-galactosidase A mutations and genotype-phenotype correlations in classical and variant phenotypes. Mol. Med. 8:306.PubMedGoogle Scholar
  21. Ginsberg, S. D., Galvin, J. E., Lee, V. M., Rorke, L. B., Dickson, D. W., Wolfe, J. H., Jones, M. Z., and Trojanowski, J. Q., 1999, Accumulation of intracellular amyloid-beta peptide (A beta 1-40) in mucopolysaccharidosis brains. J. Neuropathol. Exp. Neurol. 58:815.CrossRefPubMedGoogle Scholar
  22. Grande-Allen, K. J., Calabro, A., Gupta, V., Wight, T. N., Hascall, V. C., and Vesely, I., 2004, Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading. Glycobiology. 14:621.CrossRefPubMedGoogle Scholar
  23. Grewal, S. S., Wynn, R., Abdenur, J. E., Burton, B. K., Gharib, M., Haase, C., Hayashi, R. J., Shenoy, S., Sillence, D., Tiller, G. E., Dudek, M. E., van Royen-Kerkhof, A., Wraith, J. E., Woodard, P., Young, G. A., Wulffraat, N., Whitley, C. B., and Peters, 2005, Safety and efficacy of enzyme replacement therapy in combination with hema-topoietic stem cell transplantation in Hurler syndrome. Genet Med. 7:143.PubMedCrossRefGoogle Scholar
  24. Guffon, N., Souillet, G., Maire, I., Straczek, J., and Guibaud, P., 1998, Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J. Pediatr. 133:119.PubMedGoogle Scholar
  25. Gullingsrud, E.O, Krivit, W, and Summers, C. G., 1998, Ocular abnormalities in the mucopolysaccharidoses after bone marrow transplantation longer follow up. Ophthal. 105:1099.CrossRefGoogle Scholar
  26. Hinek, A., and Wilson, S. E., 2000, Impaired elastogenesis in Hurler disease: Dermatan sulfate accumulation linked to deficiency in elastin-binding protein and elastic fiber assembly. Am. J. Path. 156:925.PubMedGoogle Scholar
  27. Hinek, A., Braun, K. R., Liu, K., Wang, Y., and Wight, T. N., 2004, Retrovirally mediated overexpression of versican v3 reverses impaired elastogenesis and heightened prolixferation exhibited by fibroblasts from Costello syndrome and Hurler disease patients. Am. J. Pathol. 164:119.PubMedGoogle Scholar
  28. Huang, Y., Bron, A. J., Meek, K. M., Vellodi, A., and McDonald, B., 1996, Ultra-structural study of the cornea in a bone marrow-transplanted Hurler syndrome patient. Exp. Eye. Res. 62:377.CrossRefPubMedGoogle Scholar
  29. Kakavanos, R. Turner, C. T., Hopwood, J. J., Kakkis, E. D., and Brooks, D. A., 2003, Immune tolerance after long-term enzyme-replacement therapy among patients who have mucopolysaccharidosis I. Lancet. 361:1608.CrossRefPubMedGoogle Scholar
  30. Kakkis, E. D., Muenzer, J., Tiller, G, E., Waber, L., Belmont, J., Passage, M., Izykowski, B., Phillips, J., Doroshow, R., Walot, I., Hoft, R., and Neufeld, E. F., 2001, Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. 344:182.CrossRefPubMedGoogle Scholar
  31. Kinsella, M. G., Bressler, S. L., and Wight, T. N., 2004, The regulated synthesis of versican, decorin, and biglycan: Extracellular matrix proteoglycans that influence cellular phenotype. Crit. Rev. Eukaryot. Gene Expr. 14:203.CrossRefPubMedGoogle Scholar
  32. Knol, I. E., Ausems, M. G., Lindhout, D., van Diggelen, O. P., Verwey, H., Davies, J., Ploos van Amstel, J. K., Poll-The, B. T., 1999, Different phenotypic expression in relatives with Fabry disease caused by a W226X mutation. Am. J. Med. Genet. 82:436.CrossRefPubMedGoogle Scholar
  33. Krivit, W., Shapiro, E., Hoogerbrugge, P. M., and Moser, H. W., 1992, State of the art review. Bone marrow transplantation treatment for storage diseases. Bone Marrow Transplant 10 Suppl. 1:87.PubMedGoogle Scholar
  34. Li, P, Wood, T, and Thompson, J. N., 2002, Diversity of mutations and distribution of single nucleotide polymorphic alleles in the human alpha-L-iduronidase (IDUA) gene. Genet. Med. 4:420.PubMedCrossRefGoogle Scholar
  35. Lowry, R. B., and Renwick, D. H., 1971, Relative frequency of the Hurler and Hunter syndromes. N Engl J Med. 284:221.PubMedGoogle Scholar
  36. Matte, U., Yogalingam, G., Brooks, D., Leistner, S., Schwartz, I., Lima, L., Norato, D. Y., Brum, J.M., Beesley, C., Winchester, B., Giugliani, R., and Hopwood, J. J., 2003, Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Mol. Genet. Metab. 78:37.CrossRefPubMedGoogle Scholar
  37. McKusick, V. A., Kaplan, D., Wise, D., Hanley, W. B., Suddarth, S. B., Sevick, M. E., and Maumanee, A. W., 1965, The genetic mucopolysaccharidoses. Medicine. 44: 445.CrossRefPubMedGoogle Scholar
  38. Meikle, P. J., Hopwood, J. J., Clague, A. E., and Carey, W. F., 1999, Prevalence of lyso-somal storage disorders. JAMA., 281:249.CrossRefPubMedGoogle Scholar
  39. Nelson, J., 1997, Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet. 101:355.CrossRefPubMedGoogle Scholar
  40. Neufeld, E.F., and Muenzer, J., 2001, The mucopolysaccharidoses, In: The Metabolic and Molecular Bases of Inherited Diseases, Scriver, C. R., Beaudet, A.L., Sly, W. S., Valle, D., Childs, R., Kinzler, K. W., 8th ed., McGraw-Hill, New York, pp. 3421-3452.Google Scholar
  41. Peters, C., Balthazor, M., Shapiro, E. G., King, R. J., Kollman, C., Hegland, J. D., Henslee-Downey, J., Trigg, M. E., Cowan, M. J., Sanders, J., Bunin, N., Weinstein, H., Lenarsky, C., Falk, P., Harris, R., Bowen, T., Williams, T. E., Grayson, G. H., Warkentin, P., Sender, L., Cool, V. A., Crittenden, M., Packman, S., Kaplan, P., Lockman, L. A., et al., 1996, Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894.PubMedGoogle Scholar
  42. Peters, C., Shapiro, E. G., and Krivit, W., 1998, Hurler syndrome: Past, present, and future. J. Pediatr. 133:7.CrossRefPubMedGoogle Scholar
  43. Peters, C., Shapiro, E. G., Anderson, J., Henslee-Downey, P. J., Klemperer, M. R., Cowan, M. J., Saunders, E. F., deAlarcon, P. A., Twist, C., Nachman, J. B., Hale, G. A., Harris, R. E., Rozans, M. K., Kurtzberg, J., Grayson, G. H., Williams, T. E., Lenarsky, C., Wagner, J. E., and Krivit, W., 1998, Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood 91:2601.PubMedGoogle Scholar
  44. Poorthuis, B. J., Wevers, R. A., Kleijer, W. J., Groener, J.E., de Jong, J. G., van Weely, S., Niezen-Koning, K. E., and van Diggelen, O. P., 1999, The frequency of lysosomal storage diseases in The Netherlands. Hum Genet. 105:151.PubMedGoogle Scholar
  45. Rempel, B. P., Clarke, L. A., and Withers, S. G., 2005, A homology model for human α-L-iduronidase: insights into human disease, Hum. Mol. Genet. 85:28-37.Google Scholar
  46. Roubicek, M., Gehler, J., and Spranger, J., 1985, The clinical spectrum of a-L-iduronidase deficiency. Am. J. Med. Genet. 20:471.CrossRefPubMedGoogle Scholar
  47. Scott, H. S., Anson, D. S., Orsborn, A. M., Nelson, P. V., Clements, P. R., Morris, C. P., and Hopwood, J. J., 1991, Human alpha-L-iduronidase: cDNA isolation and expre-ssion. Proc. Natl. Acad. Sci. U S A 88:9695.CrossRefPubMedGoogle Scholar
  48. Scott, H. S., Bunge, S., Gal, A., Clarke, L. A., Morris, C. P., and Hopwood, J. J., 1995, Molecular genetics of mucopolysaccharidosis type I: Diagnostic, clinical, and bio-logical implications. Hum. Mutat. 6:288.CrossRefPubMedGoogle Scholar
  49. Scott, H. S., Guo, X. H., Hopwood, J. J., and Morris, C. P., 1992, Structure and sequence of the human alpha-L-iduronidase gene. Genomics, 13:1311.CrossRefPubMedGoogle Scholar
  50. Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., and Morris, C. P. 1993b, Identification of mutations in the α-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. Am. J. Hum. Genet. 53:973.Google Scholar
  51. Scott, H. S., Nelson, P. V., Litjens, T., Hopwood, J. J., and Morris, C. P., 1993, Multiple polymorphisms within the a-L-iduronidase gene (IDUA): Implications for a role in modification of MPS-I disease phenotype. Hum. Mol.Genet. 2:1471.CrossRefPubMedGoogle Scholar
  52. Slavotinek, A. M., and Biesecker, L. G., 2001, Unfolding the role of chaperones and chaperonins in human disease. Trends Genet. 17:528.CrossRefPubMedGoogle Scholar
  53. Souillet, G., Guffon, N., Maire, I., Pujol, M., Taylor, P., Sevin, F., Bleyzac, N., Mulier, C., Durin, A., Kebaili, K., Galambrun, C., Bertrand, Y., Froissart, R., Dorche, C., Gebuhrer, L., Garin, C., Berard, J., and Guibaud, P., 2003, Outcome of 27 patients with Hurler’s syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant. 31:1105.CrossRefPubMedGoogle Scholar
  54. Staba, S. L., Escolar, M. L., Poe, M., Kim, Y., Martin, P. L., Szabolcs, P., Allison-Thacker, J., Wood, S., Wenger, D. A., Rubinstein, P., Hopwood, J. J., Krivit, W., and Kurtzberg J., 2004, Cord-blood transplants from unrelated donors in patients with Hurler syndrome. N. Eng. J. Med. 350:1960.CrossRefGoogle Scholar
  55. Terlato, N. J., and Cox, G. F., 2003, Can mucopolysaccharidosis type I disease severity be predicted based on a patient’s genotype? A comprehensive review of the literature. Genet Med. 5:286.PubMedCrossRefGoogle Scholar
  56. Tsui, P. T., Bach, G., Matynia, A., Hwang, M., and Neufeld, E. F., 1995, Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS I and MPS I H/S). Hum. Mutat. 6:55.CrossRefGoogle Scholar
  57. Urban, Z., and Boyd, C. D., 2000, Elastic fiber pathologies: Primary defects in assembly and secondary disorders in transport and delivery. Am. J. Hum. Genet. 67:4.CrossRefPubMedGoogle Scholar
  58. Vellodi, A., Young, E. P., Cooper, A., Wraith, J. E., Winchester, B., Meaney, C., Ramaswami, U., and Will, A., 1997, Bone marrow transplantation for mucopoly-saccharidosis type I: Experience of two British centres. Arch. Dis. Child. 76:92.CrossRefPubMedGoogle Scholar
  59. Venturi, N., Rovelli, A., Parini, R., Menni, F., Brambillasca, F., Bertagnolio, F., Uziel, G., Gatti, R., Filocamo, M., Donati, M. A., Biondi, A., and Goldwurm, S., 2002, Hum. Mutat. 20:231.CrossRefPubMedGoogle Scholar
  60. Weisstein, J. S., Delgado, E., Steinbach, L. S., Hart, K., and Packman, S., 2004, Musculo-skeletal manifestations of Hurler syndrome. J. Pediatr. Orthop. 24:97.PubMedGoogle Scholar
  61. Whitley, C. B., Belani K. G., Chang, P. N., Summers, C. G., Blazar, B. R., Tsai, M. Y., Latchaw, R. E., Ramsay, N. K., and Kersey, J. H., 1993, Long-term outcome of Hurler syndrome following bone marrow transplantation. Am. J. Med. Genet. 46:209.CrossRefPubMedGoogle Scholar
  62. Wiesmann, U. N. and Neufeld, E. F., 1970, Scheie and Hurler syndromes: apparent identity of the biochemical defect. Science. 169:72.CrossRefPubMedGoogle Scholar
  63. Wraith, J. E., Clarke, L. A., Beck, M., Kolodny, E. H., Pastores, G. M., Muenzer, J., Rapoport, D. M., Berger, K. I., Swiedler, S. J., Kakkis, E. D., Braakman, T., Chadbourne, E., Walton-Bowen, K., and Cox G. F., 2004, Enzyme replacement therapy for Mucopolysaccharidosis I: A randomized, double-blind, placebo-controlled, multinational study of recombinant human a-L-iduronidase (Laronidase). J. Pediatr. 144:581.CrossRefPubMedGoogle Scholar
  64. Zhao, H., Keddache, M., Bailey, L., Arnold, G., and Grabowski, G., 2003, Gaucher’s disease: Identification of novel mutant alleles and genotype-phenotype relationships. Clin. Genet. 64:57.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Lorne A. Clarke
    • 1
  1. 1.Department of Medical GeneticsUniversity of British Columbia, Child and Family Research InstituteVancouverCanada

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