Cardiac manifestations of Anderson-Fabry disease in children and adolescents

Abstract

Aim: Fabry disease (Fabry) is a rare X-linked disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A. The progressive accumulation of the major substrate, globotriaosylceramide, leads to renal dysfunction and hypertrophic cardiomyopathy, which are reported to become apparent in the third decade. This study was performed to determine if signs of cardiac manifestations of Fabry are seen in younger Fabry patients.

Methods: Twenty children and adolescents of <or=18 years of age with confirmed Fabry underwent a standard 12-lead electrocardiogram (ECG), a 2-h Holter ECG, blood pressure measurements and a two-dimensional echocardiogram. Follow-up examinations were conducted for 14 patients after a mean interval of 25.9 months.

Results: At baseline, mean left ventricular mass (LVM) indexed to height (LVM/h(2.7)) was 45.0+/-2.3 and 47.0+/-3.4 g/m(2.7) in boys (n=8) and girls (n=12), respectively, and all patients had LVM/h(2.7) of >75th percentile of that in healthy controls. After a mean 26-month follow-up, 12 out of 14 patients (85.7%) showed a mean increase of 7.5+/-3.2 g/m(2.7) in LVM/h(2.7). Heart rate variability (HRV) analyses revealed that male, but not female, Fabry patients had significantly reduced HRV, reflecting a reduction in parasympathetic stimulation of the heart (p<0.05).

Conclusion: Cardiac involvement in children with Fabry is frequent and may progress even at young age.