Hostname: page-component-76fb5796d-22dnz Total loading time: 0 Render date: 2024-04-25T15:39:17.225Z Has data issue: false hasContentIssue false
  • English
  • Français

The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses

Published online by Cambridge University Press:  01 April 2009

Vlasta Fesslová ,
Paola Corti ,
Giovanna Sersale ,
Attilio Rovelli ,
Pierluigi Russo ,
Savina Mannarino ,
Gianfranco Butera  and
Rossella Parini
Vlasta Fesslová*
Affiliation:
Department of Pediatric Cardiology, Cardiovascular Center, Policlinico San Donato, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan
Paola Corti
Affiliation:
Department of Pediatrics, Bone Marrow Transplantation Unit, University of Milan-Bicocca, San Gerardo Hospital, Monza
Giovanna Sersale
Affiliation:
Department of Pediatrics, Centro “Fondazione Mariani” per le Malattie Metaboliche dell’Infanzia, University of Milan-Bicocca, San Gerardo Hospital, Monza
Attilio Rovelli
Affiliation:
Department of Pediatrics, Bone Marrow Transplantation Unit, University of Milan-Bicocca, San Gerardo Hospital, Monza
Pierluigi Russo
Affiliation:
Department of Cardiology, San Gerardo Hospital, Monza
Savina Mannarino
Affiliation:
Department of Pediatric Cardiology, Policlinico San Matteo, Pavia, Italy
Gianfranco Butera
Affiliation:
Department of Pediatric Cardiology, Cardiovascular Center, Policlinico San Donato, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan
Rossella Parini
Affiliation:
Department of Pediatrics, Centro “Fondazione Mariani” per le Malattie Metaboliche dell’Infanzia, University of Milan-Bicocca, San Gerardo Hospital, Monza
*
Correspondence to: Vlasta Fesslova, MD, Dpt. Ped.Cardiology, Cardiovascular Center, Policlinico San Donato IRCCS, Via Morandi 30, San Donato Milanese, Milano 20097, Italy. Tel: +39 02 52774 511/45; Fax: +39 02 52774 459; E-mail: cardiologiafetale@grupposandonato.it
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

To analyze cardiac involvement and its progression in mucopolysaccharidoses, and to assess the short term impact of new therapeutic strategies.

Patients and methods

We studied echocardiographically 57 patients with various types of mucopolysaccharidoses, specifically types I, II, III, IV and VI, with a median age at the diagnosis of cardiac involvement of 5 years, following them for a median of 4.6 years, with a range from 0.9 to 21.2 years. We used a scoring system, along with the so-called delta score, to quantify the severity of involvement at baseline and at last examination, and to chart their progression over time.

Results

Cases with cardiac involvement increased from 59.6% to 87.3% at the last examination. The scores increased with age, and were significantly different according to the specific type of mucopolysaccharidosis. Involvement of the mitral valve was most common, often associated with an aortic valvar anomaly and/or left ventricular hypertrophy. Patients with the first and second types had more severe involvement than those with the third or fourth types. Patients undergoing transplantation of haematopoietic stem cells seem to stabilize after an initial worsening while, in contrast, we were unable to demonstrate an effect of enzyme replacement therapy on the progression of the cardiac disease, possibly because those receiving such treatment had a higher median age, more severe cardiac disease and shorter follow-up.

Conclusions

Cardiac involvement was present early in more than a half of the patients identified as having mucopolysaccharidosis, and generally progressed, being more frequent and severe in the first and second types of the disease. Longer follow-up is needed to demonstrate any significant improvement induced by new therapies.

Keywords

lysosomal storage disordershaematopoietic stem cell transplantationenzyme replacement therapycardiac anomaliesechocardiography
Type
Original Article
Information
Cardiology in the Young , Volume 19 , Issue 2 , April 2009 , pp. 170 - 178
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Neufeld, E, Muenzer, J. The Mucopolysaccharidoses. In: Scriver C, Beaudet A, Sly W, Valle D (eds). The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York, 2001, pp 3421–3452.Google Scholar
2.Schieken, RM, Kerber, RE, Ionasescu, VV, Zellweger, H. Cardiac manifestations of the mucopolysaccharidoses. Circulation 1975; 52: 700–705.CrossRefGoogle ScholarPubMed
3.Johnson, GL, Vine, DL, Cottrill, CM, Noonan, JA. Echocardiographic mitral valve deformity in the mucopolysaccharidoses. Pediatrics 1981; 67: 401–406.CrossRefGoogle ScholarPubMed
4.Gross, DM, Williams, JC, Caprioli, C, Dominguez, B, Howell, RR. Echocardiographic abnormalities in the mucopolysaccharide storage diseases. Am J Cardiol 1988; 61: 170–176.CrossRefGoogle ScholarPubMed
5.Nelson, J, Shields, MD, Mulholland, HC. Cardiovascular studies in the mucopolysaccharidoses. J Med Genet 1990; 27: 94–100.CrossRefGoogle ScholarPubMed
6.Taylor, DB, Blaser, SI, Burrows, PE, Stringer, DA, Clarke, JTR, Thorner, P. Arteriopathy and coarctation of the abdominal aorta in children with mucopolysaccharidosis: imaging findings. Am J Roentgenol 1991; 157: 819–823.CrossRefGoogle ScholarPubMed
7.Tan, CT, Schaff, HV, Miller, FA Jr, Edwards, WD, Karnes, PS. Valvular heart disease in four patients with Maroteaux-Lamy syndrome. Circulation 1992; 85: 188–195.CrossRefGoogle ScholarPubMed
8.Wippermann, CF, Beck, M, Schranz, D, Huth, R, Michel-Behnke, I, Jungst, BK. Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses. Eur J Pediatr 1995; 154: 98–101.CrossRefGoogle ScholarPubMed
9.Dangel, JH. Cardiovascular changes in children with mucopolysaccharide storage diseases and related disorders – clinical and echocardiographic findings in 64 patients. Eur J Pediatr 1998; 157: 534–538.CrossRefGoogle ScholarPubMed
10.Mohan, UR, Hay, AA, Cleary, MA, Wrath, JE, Patel, RG. Cardiovascular changes in children with mucopolysaccharide disorders. Acta Paediatr 2002; 91: 799–804.CrossRefGoogle ScholarPubMed
11.Rigante, D, Segni, G. Cardiac structural involvement in mucopolysaccharidoses. Cardiology 2002; 98: 18–20.CrossRefGoogle ScholarPubMed
12.Donaldson, M, Pennock, C, Berry, P, Duncan, A, Cawdery, J, Leonard, J. Hurler Syndrome with cardiomyopathy in infancy. J Pediatr 1989; 114: 430–432.CrossRefGoogle ScholarPubMed
13.Hayflick, S, Rowe, S, Kavanaugh-McHugh, A, Olson, JL, Valle, D. Acute infantile cardiomyopathy as a presenting feature of mucopolysaccharidosis VI. J Pediatr 1992; 120: 269–272.CrossRefGoogle ScholarPubMed
14.Ortega, AJ, Dominguez, LC, Olive, OT, et al. Bone marrow transplantation in mucopolysaccharidosis type I, Hurler-Sheie variety. Metabolic correction and clinical results. An Esp Pediatr 1990; 33: 369–375.Google Scholar
15.Viñallonga, X, Sanz, N, Balaguer, A, Miro, L, Ortega, JJ, Casaldaliga, J. Hypetrophic cardiomyopathy in mucopolysaccharidoses: regression after bone marrow transplantation. Pediatr Cardiol 1992; 13: 107–109.CrossRefGoogle Scholar
16.Gatzoulis, MA, Vellodi, A, Redington, AN. Cardiac involvement in mucopolysaccharidoses: effects of allogeneic bone marrow transplantation. Arch Dis Child 1995; 73: 259–260.CrossRefGoogle ScholarPubMed
17.Herskhovitz, E, Young, E, Rainer, J, et al. Bone marrow transplantation for Maroteaux-Lamy syndrome (MPS VI): long-term follow-up. J Inherit Metab Dis 1999; 22: 50–62.CrossRefGoogle ScholarPubMed
18.Braunlin, E, Rose, A, Hopwood, J, Candel, R, Krivit, W. Coronary artery patency following long-term successful engraftment 14 years after bone marrow transplantation in the Hurler syndrome. Am J Cardiol 2001; 88: 1075–1077.CrossRefGoogle ScholarPubMed
19.Braunlin, EA, Stauffer, NR, Peters, CH, et al. Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol 2003; 92: 882–886.CrossRefGoogle ScholarPubMed
20.Peters, C, Steward, CG. Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 2003; 31: 229–239.CrossRefGoogle ScholarPubMed
21.Wraith, JE, Clarke, LA, Beck, M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 2004; 144: 581–588.CrossRefGoogle ScholarPubMed
22.Muenzer, J, Wraith, JE, Beck, M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis type II (Hunter syndrome). Genet Med 2006; 8: 465–473.CrossRefGoogle Scholar
23.Harmatz, P, Ketteridge, D, Giugliani, R, 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: 681–689.CrossRefGoogle Scholar
24.Henry, WL, Gardin, JM, Ware, JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation 1980; 62: 1054–1061.CrossRefGoogle ScholarPubMed
25.Miatake, K, Izumi, S, Okamoto, M, et al. Semiquantitative grading of severity of mitral regurgitation by real-time two-dimensional Doppler flow imaging technique. J Am Coll Cardiol 1986; 7: 82–88.CrossRefGoogle Scholar
26.Berger, M, Hecht, SR, Van Tosh, A, Lingam, U. Pulsed and continuous wave Doppler echocardiographic assessment of valvular regurgitation in normal subjects. J Am Coll Cardiol 1989; 13: 1540–1545.CrossRefGoogle ScholarPubMed
27.Renteria, VG, Ferrans, VJ, Roberts, WC. The heart in the Hurler syndrome: gross, histologic and ultrastructural observations in five necropsy cases. Am J Cardiol 1976; 38: 487–501.CrossRefGoogle ScholarPubMed
28.Braunlin, EA, Berry, JM, Whitley, CB. Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I. Am J Cardiol 2006; 98: 416–418.CrossRefGoogle ScholarPubMed
29.Wraith, JE. The first 5 years of clinical experience with laronidase enzyme replacement therapy for mucopolysaccharidosis I. Expert Opin Pharmacother 2005; 6: 489–506.CrossRefGoogle ScholarPubMed