AIM:The aim of this study was to document exercise capacity and serial electrocardiogram and echocardiograph findings in a cohort of Australian patients with Fabry disease, in relation to their history of enzyme replacement therapy (ERT).BACKGROUND:Fabry disease has multifactorial effects on the cardiovascular system. Most previous studies have focused on electrocardiographic and echocardiographic parameters. Exercise capacity can be used as an integrated measure of cardiovascular function and allows the effects of treatment to be monitored.METHODS:A total of 38 patients (30 men and 8 women) with Fabry disease were monitored by 12-lead electrocardiograms every 6-12 months, and by annual standardized-protocol echocardiograms. Bicycle stress tests with VO(2) max measurement and once-only 6 minutes' walk tests were also carried out in subsets of patients whose general health status allowed testing.RESULTS:Seventy per cent of patients met electrocardiogram criteria for left ventricular hypertrophy. Left ventricular hypertrophy on echocardiograph was present in 64% of patients (80% of men). Exercise capacity was reduced in patients with Fabry disease compared with that predicted from normative population data. Mild improvement in anaerobic threshold was seen in the first year of ERT (14.1 +/- 3.0 to 15.8 +/- 3.0, P = 0.02), but no consistent further increase was seen beyond the first year. Most patients had resting bradycardia, with impaired ability to increase heart rate during exercise. Serial testing on ERT showed an improvement in anaerobic threshold but no significant change in VO(2) max.CONCLUSIONS:Male patients with Fabry disease were unable to attain predicted maximal heart rate on exercise or to achieve normal exercise levels. ERT was associated with a small improvement in anaerobic threshold over the first year.

Aim: To monitor renal involvement in patients affected by Fabry disease and receiving enzyme replacement therapy (ERT). Methods: Glomerular function was examined by measuring Cystatin C (C-Cys) concentrations before and 6 (t1), 12 (t2) and 18 (t3) hours after infusion with agalsidase alfa (Replagal2) in six patients with Fabry disease. Serum C-Cys was determined by a nephelometric method. The obtained values were correlated with creatinine clearance (CrCl) and serum creatinine (sCr). Results: In one patient presenting with severe renal failure and treated with haemodialysis, the C-Cys values remained high (range, 5.22–9.50 mg/l). In one patient the basal value of 1.25 mg/l reached 2.15 mg/l due to his tubular function impairment. In the other patients, the C-Cys values were 0.87 § 0.51, 0.99 § 0.76, 1.10 § 0.69 and 0.99 § 0.42 mg/l at t0, t1, t2, and t3, respectively (normal range, 0.57–0.92 mg/l). At the same time, the CrCl values were 66.3 § 24.9, 84.3 § 29.9, 95.3 § 39.6 and 75.5 § 31.8 ml/minute/1.73 m, and sCr values were 1.25 § 0.47, 1.29 § 0.60, 1.13 § 0.66 and 1.30 § 0.56 mg/dl, respectively. Conclusions: C-Cys and CrCl seem to correlate equally well with glomerular and tubular functions. When the measured C-Cys is in the normal range, the CrCl appears better able to measure the minimal changes in renal function, but this method is disagreeable for patients and laborious. The effectiveness of ERT is limited when started late and in the presence of severe renal dysfunction. However, ERT given in the early stages of disease may prevent renal impairment and induce recovery of glomerular and tubular function.