Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler–Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry. Interrogation of echocardiography data (presence of cardiac valve regurgitation and/or stenosis; measurements of left ventricular chamber dimensions in diastole and systole, diastolic left ventricular posterior wall and interventricular septal thicknesses and ventricular systolic function (shortening fraction)) showed that mitral regurgitation was the most common and earliest finding for individuals with both severe (58.3%, median age 1.2 years) and attenuated (74.2%, median age 8.0 years) disease. Left-sided valve stenosis was also common in individuals with attenuated disease (mitral 30.3%; aortic 25%). Abnormal ventricular wall and septal thickness (Z-scores ≥2) were observed early in both phenotypes. Z-scores for diastolic left ventricular posterior wall and interventricular septal thicknesses increased with age in the severe phenotype (annualised slopes of 0.2777 [p = 0.037] and 0.3831 [p = 0.001], respectively); a similar correlation was not observed in the attenuated phenotype (annualised slopes of −0.0401 [p = 0.069] and −0.0029 [p = 0.875], respectively). Decreased cardiac ventricular systolic function (defined as shortening fraction <28%) was uncommon but, when noted, was more frequent in infants with the severe phenotype. While cardiac abnormalities occur early in both severe and attenuated mucopolysaccharidosis type I, the pattern of valve dysfunction and progression of ventricular abnormalities vary by phenotype.

We describe a case of severe aortic stenosis in a 16-year-old male with Hurler's syndrome who had prior bone marrow transplantation. The excised aortic valve leaflets showed characteristic pathologic findings of Hurler's syndrome. This is the first case report of aortic valve replacement in a patient with Hurler's syndrome treated with bone marrow transplantation that demonstrates progression of the aortic valve disease despite treatment.

We studied the cardiac conduction system in a case of Hurler syndrome. There was dense fibrosis of the supporting matrix of the sinus node and accumulation of mucopolysaccharide in the nodal cells. The bundle branches showed prominent hydropic degeneration, being encased and punctuated by dense fibrous tissue. These changes in the conduction system may predispose to the development of arrhythmias, accounting for the sudden deaths in Hurler syndrome.