Left Ventricular Aneurysm Associated With Mucopolysaccharidosis Type VI Syndrome (Maroteaux–Lamy Syndrome)
A 22-year-old man was diagnosed with mucopolysaccharidosis type VI (MPS VI) when he was 2 years old, and he developed several complications of long-standing MPS VI. He had not been treated with enzyme-replacement therapy (not an approved therapy in Canada). Because of persistent dyspnea and poor exercise tolerance (New York Heart Association class III), he was investigated for cardiac disease. He had no risk factors for coronary artery disease, his 12-lead ECG showed a normal sinus rhythm with no Q waves, and there were no elevations in serum creatine kinase-MB, troponin I, or lactate dehydrogenase. Transthoracic echocardiography showed mildly thickened aortic and mitral valves and a grade 2 left ventricle with a well-delineated, thin-walled apical aneurysm measuring 2.6×2.9 cm (Figure 1A). Review of previous echocardiograms suggested that the left ventricular aneurysm was new and therefore likely acquired rather than congenital. Left ventriculogram confirmed the presence of an apical aneurysm with normal wall motion elsewhere (Figure 1B). The cavity above the aneurysm was clearly delineated, with a peak gradient of 28 mm Hg. Coronary angiogram revealed normal origin and course of the epicardial coronary arteries with no significant stenosis (Figure 2). Left ventricular aneurysmectomy was performed via an open thoracotomy, revealing a prominent left ventricular aneurysm (Figure 3). The resected aneurysmal tissue showed a true aneurysm, with marked thinning of the ventricular wall with areas of significant fibrosis (Figure 4A and 4B). There were focal areas of chronic inflammatory infiltrates (Figure 4C), which consisted predominantly of macrophages. Electron microscopy confirmed disorganized muscle fibers and marked accumulation of electron-lucent material in macrophages (Figure 4D). Postoperatively, the patient reported moderate improvement in exercise tolerance after the aneu-rysmectomy, with normalization of left ventricular function (grade 1 left ventricle).
MPS VI, which is also known as Maroteaux–Lamy syndrome, is a lysosomal storage disease caused by the deficiency of the enzyme N-acetylgalactosamine-4-sulfatase. This enzyme is responsible for the catabolism of glycosaminoglycans, dermatan sulfate, and chondroitin sulfate, and in MPS VI, these partially degraded glycosaminoglycans accumulate in several tissues. In this case report, we present the first description of the de novo development of a primary apical left ventricular aneurysm in the setting of altered metabolism of glycosaminoglycans in a patient with MPS VI. The apical location of the aneurysm may be related to the relatively higher wall stress that the apex endures during systole. The most common cardiac manifestations of MPS VI include valvulopathy of the mitral and aortic valves leading to mixed valvular disease, which is characterized by valvular stenosis with regurgitation. However, the accumulation of proteoglycan, dermatan sulfate, and chondroitin sulfate in the myocardial interstitium may alter the extracellular matrix (which is a critical determinant of myocardial contractility) and the myocardial response to increased wall stress. This case report illustrates the importance of the extracellular matrix, particularly the proteoglycans, in maintaining cardiac structure and function.