Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

Abstract

BackgroundFabry disease (FD) is a rare disorder and one of the causes of progressive renal and cardiac dysfunction. FD results from an X-linked recessive lysosomal storage disorder caused by a defect in the gene encoding lysosomal α-galactosidase A. Although accumulation of globotriaosylceramide leads to renal and cardiac manifestations, the precise mechanisms remain unclear. Coronary microvascular dysfunction may be one of the causes of cardiac complications in FD. We aimed to assess coronary flow reserve (CFR) and the effect of enzyme replacement therapy (ERT) on coronary microvascular dysfunction.MethodsFour FD patients who had never received ERT were included. The serum asymmetric dimethylarginine (ADMA) level, as a marker of endothelial dysfunction, was measured. Two-dimensional guided M-mode echocardiography was performed to measure left ventricular wall mass. Adenosine-triphosphate stress transthoracic Doppler echocardiography was used to measure CFR before starting ERT and at 3, 6 and 12 months.ResultsAll the patients tolerated ERT without any side effects. At the baseline, two patients had impaired CFR, increased left ventricular mass index (LVMI) and elevated serum ADMA levels. Twelve months after starting ERT, CFR was increased in all patients, and LVMI and serum ADMA levels decreased in two patients. Furthermore, serum ADMA levels significantly correlated with CFR (r = −0.576, P < 0.05) and LVMI (r = 0.874, P < 0.0001).ConclusionsThe results suggest that ERT prevented the progression of cardiac abnormalities, possibly by improving coronary microvascular dysfunction. ADMA may be a useful surrogate marker in FD.

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

“…Eight mixed-ERT OS publications (including some large, long-term studies including ≤100 patients followed for ≤120 months) agreed that ERT might slow the decrease in eGFR [51,103,104,107,109,112,114,116]. One large, long-term OS publication reported that patients without proteinuria responded better to treatment than patients with overt proteinuria (109 patients followed for ≤116 months) [103].…”

“…Findings from mixed-ERT studies were reported across nine OS publications [101,104,107,109,110,112,113,114,116] including a large study in 100 patients followed for 59–64 months [114]. One OS publication showed that patients with an abnormal baseline electrocardiogram (ECG) had a statistically significant increase in LVMi, while patients with normal ECG at baseline did not experience any statistically significant change in LVMi (neither progression nor regression) with mixed-ERT treatment (6 years’ follow-up) [113].…”

Characteristics of coronary artery disease in chronic kidney disease

“…Several our clinical studies assessed CFR using transthoracic Doppler echocardiography (Fig. 2) [20, 22–24], a non-invasive and safe method that does not involve the risk of radiation exposure. Our data showed that CFR was significantly associated with the estimated glomerular filtration rate (eGFR) in hypertensive patients without a significant coronary artery stenosis (Fig.…”