Abstract
Background
This study aimed to determine cardiac findings in patients with mucopolysaccharidosis (MPS) and to assess the changes in these findings after enzyme replacement therapy (ERT).
Methods
A retrospective clinical cohort study was conducted on patients who were diagnosed with MPS between 1995 and 2018 in Hacettepe University, Division of Pediatric Metabolism. A total of 96 patients were diagnosed with MPS during the study period. Of these patients, 81 (84.3%) received ERT. Echocardiographic findings of the patients together with the 6-min walking test (6MWT) results before and after ERT were compared.
Results
Thirty-one participants (38.2%) were female, while 50 (61.8%) were male. The mean age of the participants was 11.97 ± 6.33 years (range: 1.8–30). Five patients (6.2%) had MPS type I, 14 (17.3%) had type II, 28 (34.6%) had type IVa, 33 (40.7%) had type VI and one (1.2%) had type VII. Before ERT, 69.4% of patients had mitral insufficiency (MI; mild: 40.5%, moderate: 16.5%, severe: 12.7%), 35.4% had aortic insufficiency (AI; mild: 22.8%, moderate: 12.7%) and 45.1% had tricuspid insufficiency (TI; mild: 39.2%, moderate: 2.5%). The median duration of the ERT was 3.5 years. The ERT significantly improved left ventricular hypertrophy (LVH), but all other study variables returned non-significant before and after treatment. ERT may improve LVH in MPS. Bearing in mind that MPS is a progressive disease, ERT seems to prevent significant deterioration of this ailment but is not able to reverse the already settled pathologies except for LVH. ERT is not able to reverse the damage, but provides stabilization; so it is best to initiate treatment before cardiac damage.
Acknowledgements
The authors would like to thank the patients who participated in this study. Furthermore, authors would like to thank the pediatric metabolism and pediatric cardiology teams.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Suarez-Guerrero JL, Gómez Higuera PJ, Arias Flórez JS, Contreras-García GA. [Mucopolysaccharidosis: clinical features, diagnosis and management]. Rev Chil Pediatr 2016;87:295–304.10.1016/j.rchipe.2015.10.004Search in Google Scholar PubMed
2. Braunlin EA, Berry JM, Whitley CB. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am J Cardiol 2006;98:416–8.10.1016/j.amjcard.2006.02.047Search in Google Scholar PubMed
3. Boffi L, Russo P, Limongelli G. Early diagnosis and management of cardiac manifestations in mucopolysaccharidoses: a practical guide for paediatric and adult cardiologists. Ital J Pediatr 2018;44(Suppl 2):122.10.1186/s13052-018-0560-3Search in Google Scholar PubMed
4. Mohan UR, Hay AA, Cleary MA, Wraith JE, Patel RG. Cardiovascular changes in children with mucopolysaccharide disorders. Acta Paediatr 2002;91:799–804.10.1111/j.1651-2227.2002.tb03330.xSearch in Google Scholar PubMed
5. Braunlin EA, Harmatz PR, Scarpa M, Furlanetto B, Kampmann C, et al. Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management. J Inherit Metab Dis 2011;34:1183–97.10.1007/s10545-011-9359-8Search in Google Scholar PubMed
6. Braunlin E, Mackey-Bojack S, Panoskaltsis-Mortari A, Berry JM, McElmurry RT, et al. Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: implications for assessment of therapeutic interventions in hurler syndrome. Pediatr Res 2006;59:27–32.10.1203/01.pdr.0000190579.24054.39Search in Google Scholar PubMed
7. Gross DM, Williams JC, Caprioli C, Dominguez B, Howell RR. Echocardiographic abnormalities in the mucopolysaccharide storage diseases. Am J Cardiol 1988;61:170–6.10.1016/0002-9149(88)91325-2Search in Google Scholar PubMed
8. Muenzer J. Early initiation of enzyme replacement therapy for the mucopolysaccharidoses. Mol Genet Metab 2014;111:63–72.10.1016/j.ymgme.2013.11.015Search in Google Scholar PubMed
9. Harmatz P, Ketteridge D, Giugliani R, Guffon N, Teles EL, et al. Direct comparison of measures of endurance, mobility, and joint function during enzyme-replacement therapy of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): results after 48 weeks in a phase 2 open-label clinical study of recombinant human N-acetylgalactosamine 4-sulfatase. Pediatrics 2005;115:e681–9.10.1542/peds.2004-1023Search in Google Scholar PubMed
10. Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 2006;8:465–73.10.1097/01.gim.0000232477.37660.fbSearch in Google Scholar PubMed
11. Arranz L, Aldamiz-Echevarria L. Enzyme replacement therapy in Hurler syndrome after failure of hematopoietic transplant. Mol Genet Metab Rep 2015;3:88–91.10.1016/j.ymgmr.2015.04.003Search in Google Scholar PubMed PubMed Central
12. Kilic M, Dursun A, Coskun T, Tokatli A, Ozgul RK, et al. Genotypic-phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey. Am J Med Genet A 2017;173:2954–67.10.1002/ajmg.a.38459Search in Google Scholar PubMed
13. Sprander J. Mucopolysaccharidoses. In: Kliegman R, BehrmanR, Jenson H, Stanton B, editors. Nelson textbook of pediatrics, 18th ed. Philadelphia, PA, USA: Elsevier, 2007:620–6.Search in Google Scholar
14. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344–9.10.1016/j.jclinepi.2007.11.008Search in Google Scholar PubMed
15. Leal GN, de Paula AC, Leone C, Kim CA. Echocardiographic study of paediatric patients with mucopolysaccharidosis. Cardiol Young 2010;20:254–61.10.1017/S104795110999062XSearch in Google Scholar PubMed
16. Fesslova V, Corti P, Sersale G, Rovelli A, Russo P, et al. The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses. Cardiol Young 2009;19:170–8.10.1017/S1047951109003576Search in Google Scholar PubMed
17. Chen MR, Lin SP, Hwang HK, Yu CH. Cardiovascular changes in mucopolysaccharidoses in Taiwan. Acta Cardiol 2005;60:51–3.10.2143/AC.60.1.2005049Search in Google Scholar PubMed
18. Pastores GM, Arn P, Beck M, Clarke JT, Guffon N, et al. The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. Mol Genet Metab 2007;91:37–47.10.1016/j.ymgme.2007.01.011Search in Google Scholar PubMed
19. Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, et al. Initial report from the Hunter Outcome Survey. Genet Med 2008;10:508–16.10.1097/GIM.0b013e31817701e6Search in Google Scholar PubMed
20. Scarpa M, Barone R, Fiumara A, Astarita L, Parenti G, et al. Mucopolysaccharidosis VI: the Italian experience. Eur J Pediatr 2009;168:1203–6.10.1007/s00431-008-0910-zSearch in Google Scholar PubMed
21. Parini R, Rigoldi M, Tedesco L, Boffi L, Brambilla A, et al. Enzymatic replacement therapy for Hunter disease: up to 9 years experience with 17 patients. Mol Genet Metab Rep 2015;3:65–74.10.1016/j.ymgmr.2015.03.011Search in Google Scholar PubMed PubMed Central
22. Brands MM, Oussoren E, Ruijter GJ, Vollebregt AA, van den Hout HM, et al. Up to five years experience with 11 mucopolysaccharidosis type VI patients. Mol Genet Metab 2013;109:70–6.10.1016/j.ymgme.2013.02.013Search in Google Scholar PubMed
23. Lin HY, Chuang CK, Wang CH, Chien YH, Wang YM, et al. Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: a case series. Mol Genet Metab Rep 2016;7:63–9.10.1016/j.ymgmr.2016.04.003Search in Google Scholar PubMed PubMed Central
24. Concolino D, Deodato F, Parini R. Enzyme replacement therapy: efficacy and limitations. Ital J Pediatr 2018;44(Suppl 2):120.10.1186/s13052-018-0562-1Search in Google Scholar PubMed PubMed Central
©2019 Walter de Gruyter GmbH, Berlin/Boston
