Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

Abstract

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality.The clinical examination of individuals with MPS is often difficult due to physical and, sometimes, intellectual patient limitations. The absence of precordial murmurs does not exclude the presence of cardiac disease. Echocardiography and electrocardiography are key diagnostic techniques for evaluation of valves, ventricular dimensions and function, which are recommended on a regular basis. The optimal technique for evaluation of coronary artery involvement remains unsettled.Standard medical and surgical techniques can be modified for MPS patients, and systemic therapies such as hematopoietic stem cell transplantation and enzyme replacement therapy (ERT) may alter overall disease progression with regression of ventricular hypertrophy and maintenance of ventricular function. Cardiac valve disease is usually unresponsive or, at best, stabilized, although ERT within the first few months of life may prevent valve involvement, a fact that emphasizes the importance of early diagnosis and treatment in MPS.

Experimental Impact of Mucopolysaccharidosis on Right Atrial Contractile Capacity of Skinned Fibers

“…Furthermore the fibers of patients with MPS need more calcium to achieve half maximal activation. Braunlin describes that besides the valve thickening, the subvalvular apparatus presents shortened chordae tendineae and thick papillary muscle with dysmorphic leaflets [7]. Other retrospective studies show that left ventricular hypertrophy (LVH) and diastolic dysfunction emerges at an early state whereas ventricular dilatation and systolic dysfunction occurs later [11].…”

“…Braunlin assumes that accumulation of GAGs influences the assembly of tropo-elastin. Hinek and Wilson show that this affects the structure and function of elastin [7,12]. These observations might influence cardiac atrial as well as ventricular contractility.…”

“…Cardiac involvement is described in all MPS syndromes, but is highly associated with the dermatan sulfate storing types of MPS, i.e. MPS I, II und VI and is a common and early feature, emerging silently, and contributes to early mortality and can be found in 60-90% of all patients with MPS [7].…”

“…This pathology mainly affects the left-sided valves. This valve degradation can lead to regurgitation as well as stenosis and most common the mitral valve is affected [7]. These diseases are a heterogeneous group of lysosomal storage disorders, which are caused by the absence of specific lysosomal enzymes having an incidence of 1:5000 live births [7,8].…”

Fatal and Unanticipated Cardiorespiratory Disease in a Two-Year-Old Child with Hurler Syndrome Following Successful Stem Cell Transplant

“…Cardiac disease in MPS 1 has a prevalence and severity believed to be in the range of 60-100 % of those studied and ranges from severe dilated cardiomyopathy presenting within days or weeks of birth to identification of thickened and incompetent cardiac valves in otherwise asymptomatic individuals (Leal et al 2010;Braunlin et al 2011;Wiseman et al 2012). While valvular abnormalities and coronary artery disease are most frequently documented, vascular changes in great vessels and conduction abnormalities have also been described.…”