title: Advantages of early replacement therapy for mucopolysaccharidosis type VI: echocardiographic follow-up of siblings.
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.
authors: 1 Serviço de Ecocardiografia do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors: Gabriela N
authors: GN
authors: Leal
authors: 2 Serviço de Genética do Hospital Municipal da Criança de Guarulhos, Brazil.
authors: Ana C
authors: AC
authors: de Paula
authors: 1 Serviço de Ecocardiografia do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors: Samira S
authors: SS
authors: Morhy
authors: 3 Serviço de Ecocardiografia do Instituto de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors: José L
authors: JL
authors: Andrade
authors: 4 Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors: Chong A
authors: CA
authors: Kim
mesh_terms: D001022:Aortic Valve Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D016022:Case-Control Studies; D002648:Child; D061345:Early Medical Intervention; D004452:Echocardiography; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D009087:Mucopolysaccharidosis VI / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D035781:Siblings; D020257:Ventricular Remodeling
chemical_list: D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human