Unexpected coronary artery findings in mucopolysaccharidosis. Report of four cases and literature review

Abstract

The mucopolysaccharidosis syndromes are a group of lethal inherited disorders affecting multiple organ systems by the progressive deposition of glycosaminoglycan. Advances in treatment such as enzyme replacement and hematopoietic stem cell transplantation have significantly improved the outcome of these disorders. An in-depth understanding of the pathophysiology of heart disease in these disorders is essential since death from cardiac causes continues to be common. Epicardial coronary artery luminal narrowing from myointimal proliferation and glycosaminoglycan deposition is well described in severe mucopolysaccharidosis type I [Hurler syndrome, mucopolysaccharide IH] but poorly understood in other "non-Hurler" phenotypes of these disorders. Given the rarity of these conditions, autopsy specimens are uncommon. Tissue from epicardial coronary arteries from autopsies of four patients with non-Hurler mucopolysaccharidosis (attenuated type I, type IIIA, type IIIC, and type VI) who had died after hematopoietic cell transplantation (within 1 month in three cases; after 5 years in the fourth) was examined by light microscopy. Unexpectedly, near-normal coronary arteries were observed in the patient with attenuated mucopolysaccharidosis type I, while the coronaries from patients with type IIIA, IIIC, and VI demonstrated classic histologic features of glycosaminoglycan deposition. The most severe findings were found in the MPS IIIC patient who had 5 years of full donor engraftment after transplantation. Our current understanding of the cardiac manifestations of the mucopolysaccharidoses fails to explain why near-normal coronary arteries may be observed when abnormalities would be most likely to be expected and, conversely, why significant histopathology is present when it would be least expected. Identification of downstream effects of glycosaminoglycan deposition may identify other metabolites or metabolic pathways that are important in the clinicopathologic manifestations of these diseases. The mucopolysaccharidosis diseases are a group of inherited disorders affecting multiple organ systems by the progressive deposition of glycosaminoglycan. Severe coronary artery disease is well recognized in severe type I mucopolysaccharidosis (Hurler syndrome), but unexpected coronary artery disease occurs in other, "non-Hurler" mucopolysaccharidoses. Factors responsible for the development of coronary pathology in the mucopolysaccharidoses remain elusive.