Mucopolysaccharidosis type II or Hunter syndrome is the only mucopolysaccharide storage disease to be inherited as an X-linked recessive disorder. Deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS; EC 3.1.6.13) is the primary defect in MPS I. As is seen with most X-linked potentially lethal conditions, allelic heterogeneity is significant and thus most families have individual or “private” mutations at the iduronate-2-sulfatase locus. In addition, unlike other LSDs, there is considerable heterogeneity in the molecular mechanisms underlying iduronate-2-sulfatase gene alteration in this condition. As such, this disorder, as with most of the MPSs, shows considerable clinical heterogeneity with the clinical phenotype spanning a spectrum of disease severity from early-onset childhood lethal disease to attenuated disease leading to a near normal life expectancy (Neufeld and Muenzer, 2001). In addition, patients with severe MPS II can have atypical symptomatology which likely relates to more complex genomic rearrangements underlying the disease pathogenesis. The incidence of MPS II appears to be variable in populations which have been studied, and range from 1 in 165,000 (Western Australia) to 1 in 34,000 (Israel) male live births; issues related to incomplete ascertainment in populations is noted in most studies (Lowry and Renwick, 1971; Schaap and Bach, 1980; Lowry et al., 1990; Poorthuis et al., 1999; Nelson, 1997; Meikle et al., 1999; Nelson et al., 2003). Therefore it is likely that MPS II is a panethnic disorder with an incidence in the order of 1 in 75,000 male live births. Increased incidence is expected to be seen in small populations where a founder effect would be anticipated.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Archer, I. M., Harper, P. S., and Wusterman, F.S., 1982, Multiple forms of iduronate-2-sulfatase in human tissues and body fluids. Biochem. Biophys. Acta. 708:134.
Bergstrom, S. K, Quinn, J. J., Greenstein, R., and Ascensao, J., 1994, Long-term follow-up of a patient transplanted for Hunter’s disease type IIB: A case report and literature review. Bone Marrow Transplant. 14:653.
Broadhead, D. M., Kirk, J. M., Burt, A. J., Gupta, V., Ellis, P. M., and Besley, G. T. N., 1986, Full expression of Hunter’s disease in a female with an X-chromosome deletion leading to non-random inactivation. Clin. Genet. 30:392.
Clarke, J. T. R., Greer, W. L., Strasberg, P. M., Pearce, R. D., Skomorowski, M. A., and Ray, P. N., 1991, Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl. Am. J. Hum. Genet. 49:289.
Flomen, R. H., Green, E. P., Green, P. M., Bentley, D. R., and Giannelli, F., 1993, Determination of the organisation of coding sequences within the iduronate sulphate sulphatase (IDS) gene. Hum. Mol. Genet. 2:5.
Froissart, R., Moreira da Silva, I., Guffon, N., Bozon, D., and Maire, I., 2002, Mucopoly-saccharidosis type II-genotype/phenotype aspects. Acta. Paediatr. Suppl. 91:82.
Guffon, N., Froissart, R., Philippe, N., and Maire, I., 2001, Outcome of bone marrow transplantation in eight patients with Hunter disease. J. Inherit. Metab. Dis. 24(Suppl2):172
Hunter, C., 1917, A rare disease in two brothers. Proc. R. Soc. Med. 10:104.
Hurler, G., 1919, Über einen Typ multipler Abartungen, vorwiegend am Skelettsystem. Zeitschrift für Kinderheilkunde. 24:220.
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.
Lagerstedt, K., Carlberg, B. M., Karimi-Nejad, R., Kleijer, W. J., and Bondeson, M. L., 2000, Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): Identification of a fusion transcript including sequences from the gene W and the IDS gene. Hum. Mutat. 15:324.
Li, P., Thompson, J. N., Hug, G., Huffman, P., and Chuck, G., 1996, Biochemical and molecular analysis in a patient with the severe form of Hunter syndrome after bone marrow transplantation. Am. J. Med. Genet. 64:531.
Lowry, R. B., and Renwick, D. H., 1971, Relative frequency of the Hurler and Hunter syndromes. N. Engl. J. Med. 284:221.
Lowry, R. B., Applegarth, D. A., Toone, J. R., MacDonald, E., and Thunem, N. Y., 1990, An update on the frequency of mucopolysaccharide syndromes in British Columbia. Hum. Genet. 85:389.
Lualdi, S., Regis, S., Di Rocco, M., Corsolini, F., Stroppiano, M., Antuzzi, D., and Filocamo, M., 2005, Characterization of iduronate-2-sulfatase gene-pseudogene recombinations in eight patients with Mucopolysaccharidosis type II revealed by a rapid PCR-based method. Hum. Mutat. 25:491.
McKinnis, E. J., Sulzbacher, S., Rutledge, J. C., Sanders, J., and Scott C. R., 1996, Bone marrow transplantation in Hunter syndrome. J. Pediatr. 129:145.
Meikle, P. J., Hopwood, J. J., Clague, A. E., and Carey, W. F., 1999, Prevalence of lysosomal storage disorders. JAMA 281:249.
Millat, G., Froissant, R., Maire, I., and Bozon, D., 1997, Characterization of iduronate sulfatase mutants affecting N-glycosylation sites and the cysteine-84 residue. Biochem. J. 326:243.
Mossman, J., Blunt, S., Stephens, R., Jones, E. E., and Pembrey, M., 1983, Hunter’s disease in a girl: Association with X:5 chromosomal translocation disrupting the Hunter gene. Arch. Dis. Child. 58:911.
Muenzer, J., Lamsa, J. C., Garcia, A., Dacosta, J., Garcia, J., Treco, D. A., 2002, Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): A preliminary report. Acta. Paediatr. Suppl. 91:98.
Nelson, J., 1997, Incidence of the mucopolysaccharidoses in Northern Ireland. Hum. Gen. 101:355.
Nelson, J., Crowhurst, J., Carey, B., and Greed, L., 2003, Incidence of the mucopoly-saccharidoses in Western Australia. Am. J. Med. Gen. 123:310.
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.
Parkinson-Lawrence, E., Turner, C., Hopwood, J., and Brooks, D., 2005, Analysis of normal and mutant iduronate-2-sulphatase conformation. Biochem. J. 386:395.
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.
Rathmann, M., Bunge, S., Beck, M., Kresse, H., Tylki-Szymanska, A., and Gal, A., 1996, Mucopolysaccharidosis type II (Hunter syndrome): Mutation “hot spots” in the iduronate-2-sulfatase gene. Am. J. Hum. Genet. 59:1202.
Rathmann, M., Bunge, S., Steglich, C., Schwinger, E., and Gal, A., 1995, Evidence for an iduronate-sulfatase pseudogene near the functional Hunter syndrome gene in Xq27.3-q28. Hum Genet. 95:34.
Sapadin, A. N., and Friedman, I. S., 1998, Extensive Mongolian spots associated with Hunter syndrome. J. Am. Acad. Derm. 39:1013.
Schaap, T., and Bach, G., 1980, Incidence of mucopolysaccharidoses in Israel: Is Hunter disease a ‘Jewish disease’? Hum. Genet. 56:221.
Sukegawa, K., Matsuzaki, T., Fukuda, S., Masuno, M., Fukao, T., Kokuryu, M., Iwata, S., Tomatsu, S., Orii, T., and Kondo, N., 1998, Brother/sister siblings affected with Hunter disease: Evidence for skewed X chromosome inactivation. Clin. Genet. 52:96.
Timms, K. M., Bondeson, M. L., Ansari-LarI, M. A., Lagerstedt, K., Muzny, D. M., Dugan-Rocha, S. P., Nelson, D. L., Pettersson, U., and Gibbs, R. A., 1997, Molecular and phenotypic variation in patients with severe Hunter syndrome. Hum. Mol. Genet. 6:479.
Timms, K. M., Lu, F., Shen, Y., Pierson, C. A., Muzny, D. M., Gu, Y., Nelson, D. L., Gibbs, R. A., 1995, 130 kb of DNA sequence reveals two new genes and a regional duplication distal to the human iduronate-2-sulfate sulfatase locus. Genome Res. 5:71.
Vafiadaki, E., Cooper, A., Heptinstall, L. E., Hatton, C. E., Thornley, M., and Wraith, J. E., 1998, Mutation analysis in 57 unrelated patients with MPS II (Hunter’s disease). Arch. Dis. Child. 79:237.
Vellodi, A., Young, E., Cooper, A., Lidchi, V., Winchester, B., and Wraith, J. E., 1999, Long-term follow-up following bone marrow transplantation for Hunter disease. J. Inherit. Metab. Dis. 22:638.
Wilson, P. J., Morris, C. P., Anson, D. S., Occhiodoro, T., Bielicki, J., Clements, P. R., and Hopwood, J. J., 1990, Hunter syndrome: Isolation of an iduronate-2-sulfatase cDNA clone and analysis of patient DNA. Proc. Nat. Acad. Sci. 87:8531.
Wilson, P. J., Suthers, G. K., Callen, D. F., Baker, E., Nelson, P. V., Cooper, A., Wraith, J. E., Sutherland, G. R., Morris, C. P., and Hopwood, J. J., 1991, Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome. Hum. Genet. 86:505.
Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., and Malcolm, S., 1992, Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: A consequence of twinning. Am. J. Med. Genet. 44:834.
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.
Wraith, J. E., Cooper, A., Thornley, M., Wilson, P. J., Nelson, P. V., Morris, C. P., and Hopwood, J. J., 1991, The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II-Hunter syndrome). Hum. Genet. 87:205.
Young, I. D., and Harper, P. S., 1979, Long-term complications in Hunter’s syndrome. Clin. Genet. 16:125.
Young, I. D., and Harper, P. S., 1982, Mild form of Hunter’s syndrome: Clinical delineation based on 31 cases. Arch. Dis. Child. 57:828.
Young, I. D., and Harper, P. S., 1983, The natural history of the severe form of Hunter’s syndrome: a study based on 52 cases. Dev. Med. Child Neurol. 25:481.
Young, I. D., Harper, P. S., Archer, I. M., and Newcombe, R. G., 1982b, A clinical and genetic study of Hunter’s syndrome. 1. Heterogeneity. J. Med. Gen. 19:401.
Young, I. D., Harper, P. S., Newcombe, R. G., and Archer, I. M., 1982a, A clinical and genetic study of Hunter’s syndrome. 2. Differences between the mild and severe forms. J. Med. Gen. 19:408.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Clarke, L.A. (2007). Mucopolysaccharidosis II (Hunter Syndrome). In: Lysosomal Storage Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-70909-3_25
Download citation
DOI: https://doi.org/10.1007/978-0-387-70909-3_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-70908-6
Online ISBN: 978-0-387-70909-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)