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Advantages of early replacement therapy for mucopolysaccharidosis type VI: echocardiographic follow-up of siblings

Published online by Cambridge University Press:  05 March 2013

Gabriela N. Leal ,
Ana C. de Paula ,
Samira S. Morhy ,
José L. Andrade  and
Chong A. Kim
Gabriela N. Leal*
Affiliation:
Serviço de Ecocardiografia do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
Ana C. de Paula
Affiliation:
Serviço de Genética do Hospital Municipal da Criança de Guarulhos, Brazil
Samira S. Morhy
Affiliation:
Serviço de Ecocardiografia do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
José L. Andrade
Affiliation:
Serviço de Ecocardiografia do Instituto de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
Chong A. Kim
Affiliation:
Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
*
Correspondence to: G. N. Leal, Rua Caramurú 173, apto 121, Chácara Inglesa, CEP 04138 000, São Paulo, SP, Brazil. Tel: 55 11 9958 03 34; Fax: 55 11 2578 76 73; E-mail: gnleal@gmail.com
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Abstract

Mucopolysaccharidosis type VI (Marateaux–Lamy syndrome) is an autosomal recessive disorder caused by deficient activity of the enzyme N-acetylgalactosamine-4-sulphatase (arylsulphatase B). Cytoplasmic vacuoles full of dermatan sulphate are observed in endothelial cells, myocyte, and fibroblasts, compromising the function of cardiovascular structures and contributing significantly towards morbidity and mortality. The primary objective of this study was to assess the advantages of early replacement therapy with recombinant human arylsulphatase B through the echocardiographic follow-up of sisters who started treatment at quite different ages: one at 9 years and the other at 1 year and 7 months. The older sibling showed striking mitral and aortic valve compromise when she was only 2 years old and finally needed cardiac surgery at the age of 8, even before starting enzyme replacement. Differently, the younger one has developed only mild mitral and aortic lesions throughout the follow-up period of 3 years. The two siblings had left ventricle cardiomyopathy, but partial reverse remodelling was induced by enzyme replacement therapy in both cases. The younger sibling has never received any cardiovascular drugs, whereas the older one has been using β-blockers and diuretics in addition to enzyme therapy to cope with heart failure. Comparing the outcomes of these two sisters with a very aggressive phenotype of mucopolysaccharidosis type VI, the conclusion was that early onset of therapy may slow down the disease progression and prevent severe cardiac lesions to be established. Moreover, patients’ compliance is essential for the success of treatment, as sequential echocardiographic evaluation demonstrated worsening of some cardiac lesions whenever infusions were missed.

Keywords

Mucopolysaccharidosis type VIechocardiographyearly replacement therapy
Type
Original Articles
Information
Cardiology in the Young , Volume 24 , Issue 2 , April 2014 , pp. 229 - 235
Copyright
Copyright © Cambridge University Press 2013 

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References

1. Muenzer, J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr 2004; 44: 27–34.Google Scholar
2. Leal, GN, de Paula, AC, Leone, C, Kim, CA. Echocardiographic study of paediatric patients with mucopolysaccharidosis. Cardiol Young 2010; 20: 254–261.Google Scholar
3. Mohan, UR, Hay, AA, Cleary, MA, Wraith, JE, Patel, RG. Cardiovascular changes in children with mucopolysaccharide disorders. Acta Paediatr 2002; 91: 799–804.Google Scholar
4. Guertl, B, Noehammer, C, Hoefler, G. Metabolic cardiomyopathies. Int J Exp Pathol 2001; 81: 349–372.Google Scholar
5. Braulin, E, Rosenfeld, H, Kampmann, C, et al. MPS VI Study Group. Enzyme replacement therapy for mucopolysaccharidosis VI: long term cardiac effects of galsulfatase (Naglazyme) therapy. Inherit Metab Dis 2012, [Epub ahead of print].Google Scholar
6. Brands, MM, Frohn-Mulder, IM, Hagemans, ML, et al. Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement in 24 children with MPS I, II and VI. J of Inherit Metab Dis 2012 Jan 26 [Epub ahead of print].Google Scholar
7. Fesslova, V, Corti, P, Sersale, G, et al. The natural course and the impact of therapies of cardiac involvement in mucopolysaccharidosis. Cardiol Young 2009; 19: 170–178.Google Scholar
8. Auclair, D, Hopwood, JJ, Brooks, DA, Lemontt, JF, Crawley, AC. Replacement therapy in mucopolysaccharidosis type VI: advantages of early onset of therapy. Mol Genet Metab 2003; 78: 163–174.Google Scholar
9. Giugliani, R, Federhen, A, Rojas, MV, et al. Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment. Genet Mol Biol 2010; 33: 589–604.Google Scholar
10. Dubois, D, Dubois, EF. A formula to estimate the approximate surface area if height and weight are known. Arch Intern Med 1916; 17: 863–871.Google Scholar
11. Kampmann, C, Wiethoff, CM, Wenzel, A, et al. Normal values of M mode echocardiographic measurements of more than 2000 healthy infants and children in central Europe. Heart 2000; 83: 667–672.Google Scholar
12. Carvalho, ACC, Almeida, DR, Lopes, AA. Diagnóstico, Avaliação e Terapêutica da Hipertensão Pulmonar. In: Lopes AA (ed.). Diretrizes da Sociedade Brasileira de Cardiologia, 2005; 20–29. [www.publicacoes.cardiol.br/consenso/2005/039.asp].Google Scholar
13. Zoghbi, WA, Sarano, ME, Foster, E, et al. Recommendation for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003; 16: 777–802.Google Scholar
14. Crawley, AC, Niedzielski, KH, Isaac, EL, Davey, RC, Byers, S, Hopwood, JJ. Enzyme replacement therapy from birth in a feline model of mucopolysaccharidosis type VI. J Clin Invest 1997; 99: 651–662.CrossRefGoogle Scholar
15. Neufeld, EF, Muenzer, J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The Metabolic and Molecular Bases of Inherited Diseases, 7th edn. McGray-Hill, New York, 1995, pp. 2465–2494.Google Scholar
16. McGill, JJ, Inwood, AC, Coman, DJ, et al. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age: a sibling control study. Clin Genet 2010; 77: 492–498.Google Scholar
17. Scarpa, M, Barone, R, Fiumara, A, et al. Mucopolysaccharidosis VI: the Italian experience. Eur J Pediatr 2009; 168: 1203–1206.Google Scholar
18. Braulin, EA, Harmatz, PR, Scarpa, M, et al. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis 2011; 34: 1183–1197.Google Scholar
19. Misfeld, M, Sievers, HH. Heart valve macro and microstructure. Philos Trans R Soc Lond B Biol Sci 2007; 362: 1421–1436.Google Scholar
20. Decker, C, Yu, Z-F, Giugliani, R, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase. J Pediatr Rehabil Med 2010; 3: 89–100.Google Scholar