Mucopolysaccharidoses And Alpha-mannosidosis Management: Cardiology

The session begins with an overview of lysosomal storage diseases, distinguishing MPS—which involves glycosaminoglycan (GAG) accumulation—from alpha-mannosidosis, which involves mannose-rich oligosaccharide buildup. These normally occurring molecules become pathogenic when not broken down due to enzyme deficiencies, leading to progressive, multisystem involvement.

Prof. Braunlin discusses how cardiac issues vary depending on the MPS subtype, mutation severity, treatment status, and age of onset. Accumulation of dermatan sulfate, common in MPS types I, II, VI, and VII, is particularly damaging to heart valves. Mitral and aortic regurgitation are the most frequent findings, with valve disease often progressing to stenosis in adulthood. Although enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have improved survival and cardiac function, they do not reverse established valve disease. Early treatment initiation significantly reduces severity, a fact underscored by contrasting case studies of siblings treated at different ages.

The coronary arteries are also affected, particularly in MPS I, where early-onset thickening and occlusion can occur. These changes are diffuse and difficult to detect, often invisible even to angiography, and can lead to sudden cardiac death. Encouragingly, long-term survival following HSCT and ERT suggests that these interventions may slow coronary artery disease progression.

The myocardium and conduction system are other vulnerable components. Cardiomyopathy and decreased ventricular function can be improved with ERT if diagnosed early. However, conduction abnormalities such as complete heart block may occur years after treatment, likely due to scarring. Aortic root dilation is a common feature across MPS types but rarely requires surgical intervention.

Turning to alpha-mannosidosis, Prof. Braunlin notes that cardiac involvement appears infrequent and poorly documented. Natural history studies have reported heart murmurs and occasional valve or conduction abnormalities, but overall prevalence is low. However, due to small sample sizes and limited follow-up, this remains an area of unmet need.

Prof. Braunlin concludes by recommending structured cardiac evaluations—including echocardiograms, EKGs, and biomarkers—at diagnosis and before major procedures. She emphasizes the critical importance of early diagnosis and multidisciplinary care in improving long-term cardiac outcomes for patients with storage diseases.

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