Postmortem studies on a patient with mucopolysaccharidosis type I: histopathological findings after one year of enzyme replacement therapy.

Deficiency of lysosomal α-L-iduronidase results in systemic accumulation of glycosaminoglycans (GAGs). Cardiac lesions due to accumulation of GAGs include hypertrophic cardiomyopathy, valvular insufficiency/stenosis, and coronary artery stenosis due to intimal proliferation. Cardiac dysfunction is one of the most common causes of death in patients with mucopolysaccharidosis type I (MPS I). Enzyme replacement therapy (ERT) with laronidase has shown clear effects in reduction of hepatomegaly and it has been unclear whether ERT could improve or prevent the cardiac lesions. Postmortem findings in a 3 1/2-year-old boy diagnosed with MPS I at age 2 years are described. He received ERT with laronidase at 100 U/kg/week for one year. He suddenly developed cardiorespiratory failure and died the next day after C2-3 spinal surgery for instability. Postmortem examination showed hypertrophic cardiomyopathy, severe aortic valve and mitral valve thickening with shortened chordae, and endocardial fibroelastosis. Histology of the cardiac tissue revealed increased perivascular and interstitial connective tissue in the myocardium and intimal thickening causing stenosis in the cardiac vessels. Electron-microscopic (EM) studies of the thickened endocardium revealed numerous histiocytes with enlarged lysosomes. EM examination of the liver and the cardiac muscle revealed no accumulation of GAGs. ERT with laronidase showed clear effects in removing GAGs from the liver and the cardiac muscle. However, it did not show a clear effect on the thickened endocardium, myocardial perivascular and interstitial connective tissue or intimal thickening in the epicardial vessels.