Cardiac characteristics and natural progression in Taiwanese patients with mucopolysaccharidosis III

Abstract

Background Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulfate. Cardiac abnormalities have been observed in patients with all types of MPS except MPS IX, however few studies have focused on cardiac alterations in patients with MPS III. Methods We reviewed medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III (five with IIIA, 20 with IIIB, and one with IIIC; 14 males and 12 females; median age, 7.4 years; age range, 1.8–26.5 years). The relationships between age and each echocardiographic parameter were analyzed. Results Echocardiographic examinations ( n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (31%), followed by aortic regurgitation (19%). However, most of the cases of valvular heart disease were mild. Three (12%), five (19%) and five (19%) patients had mitral valve prolapse, a thickened interventricular septum, and asymmetric septal hypertrophy, respectively. The severity of aortic regurgitation and the existence of valvular heart disease, aortic valve abnormalities and valvular stenosis were all positively correlated with increasing age ( p < 0.05). Z scores > 2 were identified in 0, 38, 8, and 27% of left ventricular mass index, interventricular septal end-diastolic dimension, left ventricular posterior wall end-diastolic dimension, and aortic diameter, respectively. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia ( n = 3), sinus bradycardia ( n = 2), and sinus tachycardia ( n = 1). Six patients with MPS IIIB had follow-up echocardiographic data at 1.9–18.1 years to compare with the baseline data, which showed some patients had increased thickness of the interventricular septum, as well as more patients had valvular abnormalities at follow-up. Conclusions Cardiac involvement in MPS III is less common and milder compared with other types of MPS. The existence of valvular heart disease, aortic valve abnormalities and valvular stenosis in the patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease.

Natural progression of cardiac features and long-term effects of enzyme replacement therapy in Taiwanese patients with mucopolysaccharidosis II

“…The presence of diastolic dysfunction was indicated by a reversed E/A ratio (E/A ratio < 1). The severity of valvular stenosis and regurgitation was evaluated and graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe), according to the European Society of Cardiology guidelines [ 37 – 40 ]: mild aortic stenosis (AS) = a valve area > 1.5 cm 2 and a mean gradient < 30 mmHg; moderate AS = a valve area of 1.0–1.5 cm 2 and a mean gradient of 30–50 mmHg; severe AS = a valve area < 1.0 cm 2 and a mean gradient > 50 mmHg; mild mitral stenosis (MS) = a valve area > 1.5 cm 2 and a mean gradient < 5 mmHg; moderate MS = a valve area between 1.0–1.5 cm 2 and a mean gradient between 5–10 mmHg; and severe MS = a valve area < 1.0 cm 2 and a mean gradient > 10 mmHg. Because of the high frequency of physiological tricuspid regurgitation in the general population, we did not regard tricuspid regurgitation as a pathological finding in this study.…”

Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses

“…The major storage products of MPS III and MPS IV are heparan sulfate and keratan sulfate, respectively. Therefore, cardiac lesions may be less prominent in patients with MPS III and IV than in those with MPS I, II, and VI [14,15,41].…”

“…Existence of diastolic dysfunction was indicated by a reversed E/A ratio (E/A ratio <1). The severity of valvular stenosis and regurgitation was assessed and graded as follows: 0 (none), 1 (mild), 2 (moderate), and 3 (severe), based on the European Society of Cardiology guidelines [12][13][14][15]35,36]: mild aortic stenosis (AS) = a valve area > 1.5 cm 2 and a mean gradient < 30 mmHg; moderate AS = a valve area of 1.0-1.5 cm 2 and a mean gradient of 30-50 mmHg; severe AS = a valve area < 1.0 cm 2 and a mean gradient > 50 mmHg; mild mitral stenosis (MS) = a valve area > 1.5 cm 2 and a mean gradient < 5 mmHg; moderate MS = a valve area between 1.0-1.5 cm 2 and a mean gradient between 5-10 mmHg; and severe MS = a valve area < 1.0 cm 2 and a mean gradient >10 mmHg. Because the frequency of physiological tricuspid regurgitation is high in the general population, we did not include tricuspid regurgitation as a pathological finding in this study.…”

“…Patients with all MPS types suffer from cardiac abnormalities, including cardiac hypertrophy, cardiac valve thickening, and valvular regurgitation and stenosis. The deformed valves with mitral or aortic leaflet thickening and calcification may lead to valvular stenosis or regurgitation [4][5][6][7][8][9][10][11][12][13][14][15]. GAG accumulation in the spongiosa of cardiac valves, myointima of coronary arteries, and myocardium has been associated with cardiomyopathy and valve defects [16].…”

Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy

“…Aortic root dilatation is frequently observed in animal models of MPS I, leading to the effacement of the sinotubular ridge [ 8 ]. Some studies have reported that aortic root dilatation may appear in various types of MPS patients, especially in those with MPS IVA [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”