Cardiac disease in children and young adults with various lysosomal storage diseases: Comparison of echocardiographic and ECG changes among clinical groups

Abstract

Background: Lysosomal storage disease (LSD) is a rare inherited disease group. Consecutively there are few data on cardiac changes in mucopolysaccharidosis (MPS), Anderson Fabry disease (AFD), and other LSD (oLSD) including Pompe disease (PD) and Danon disease (DD), I-cell disease ICD and mucolipidosis III (ML III).

Methods: Between 1994 and 2011, we identified 39 patients with LSD: 25 with MPS, 8 with AFD, and 6 with oLSD including PD (1), ML III (2), DD (1), and ICD (2) at our institution fulfilling the inclusion criteria of at least one echocardiogram and ECG.

Results: Median age was 11.4 years (range: 2-27), 22 were females (56%). Normal echocardiograms were present in 12 patients (31%): 4 with MPS (16%), 7 AFD (88%), and 1 oLSD (17%). Valvular heart disease was present in 23 patients (59%) occurring more often in MPS (76%) and oLSD (67%) than in AFD (0%) (p < 0.001). The most common ECG abnormality was a short PR interval in 10 of 35 patients (29%) occurring in all LSD groups. Median follow-up was 5.8 (0.2-22.2) years showing diminished 5-year survival compared to an age-matched group. However, no patient died due to a cardiac cause and no cardiovascular intervention was necessary.

Conclusion: Echocardiographically detectable cardiovascular involvement in children with LSD is mostly confined to MPS and oLSD. Valve thickening in echo and a short PR interval in the ECG are the most frequent abnormalities. Routine repeat assessment is recommended in LSD. However, significant cardiac disease necessitating cardiac intervention is rare during a short follow-up.

Keywords: Anderson Fabry; Cardiovascular involvement; Lysosomal storage disease; Mucopolysaccharidosis.

Fig. 1

15-Year old patient with Danon disease: parasternal long axis view with massive hypertrophy (panel a) measuring 39 mm. The 4-chamber view (Fig. 1b) shows the relation to the size of the right ventricle. In panel c, the ECG of this patient is shown with marked signs of left ventricular hypertrophy. LA = left atrium; LV = left ventricle; AO = aorta; RA = right atrium.

Fig. 1

15-Year old patient with Danon disease: parasternal long axis view with massive hypertrophy (panel a) measuring 39 mm. The 4-chamber view (Fig. 1b) shows the relation to the size of the right ventricle. In panel c, the ECG of this patient is shown with marked signs of left ventricular hypertrophy. LA = left atrium; LV = left ventricle; AO = aorta; RA = right atrium.

Fig. 2

Example of an 18-year old woman with mucopolysaccharidosis. This shows the apical 4-chamber view (apex down) with the arrow pointing to the thickened mitral valve. No progression or regression of valvular changes after 2 years of enzyme replacement therapy was observed. LA = left atrium; LV = left ventricle; RV = right ventricle.

Fig. 3

14-Year old patient with mucopolysaccharidosis Type II (hunter disease). LA = left atrium; LV = left ventricle.

Fig. 4

Kaplan–Meier curve of the survival of the MPS, AFD and oLSD patients compared to an age and sex matched white American normal population. MPS = mucopolysaccharidosis; AFD = Anderson Fabry disease; oLSD = other lysosomal storage disease.