Effects of bone marrow transplantation on the cardiovascular abnormalitiesin canine mucopolysaccharidosis VII

The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage d iseases resulting from defective catabolism of glycosaminoglycans (GAGs). E chocardiographic abnormalities in dogs with MPS type VII (Sly syndrome, bet a-glucuronidase deficiency) included mitral valve thickening and insufficie ncy, large aortic dimensions in both the long and short axes, and thickened aortic valves. Grossly, at post mortem examination, there was nodular thic kening of the mitral valve, a prominent ductus diverticulum, and a dilated aorta with thickened walls. Histologically, cytoplasmic vacuolation was see n in cells of the mitral valves, coronary arteries, and aorta. By electron microscopy, the cells of the mitral valve were packed with electron-lucent cytoplasmic vacuoles. The mean residual activity of beta-glucuronidase in t he aorta and myocardium was <1% of normal, the mean hexosaminidase A activi ty >2.5 times normal, and the mean GAG concentrations more than twice norma l. In three MPS VII dogs that received heterologous BMT at 6 weeks of age, the echocardiographic abnormalities were improved, and the histopathologic and ultrastructural pathology was reduced. In the aorta and myocardium, the mean beta-glucuronidase activity of the BMT group was 4.5% and 11% of norm al, respectively, and the hexosaminidase A activity and GAG concentrations were normalized.