AbstractMucopolysaccharidosis 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.
Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI: 10-Year follow up
