BACKGROUND: Fabry disease is an X-linked disease caused by a deficiency in the activity of the lysosomal enzyme alpha-galactosidase A. Affected individuals typically develop left ventricular hypertrophy (LVH) among other pathologies. OBJECTIVE: The purpose of the present study was to investigate the effect of >or=12 months of enzyme replacement therapy (ERT) with agalsidase alfa on LV mass (LVM) in men and women with Fabry disease. METHODS: This was a retrospective, blinded, pooled analysis of data from several studies assessing the effect of ERT with agalsidase alfa on LVM in patients with Fabry disease with baseline LVH. Men and women aged >or=18 years with a confirmed diagnosis of Fabry disease who had received >or=36 months of ERT with agalsidase alfa were eligible, provided they had a baseline echocardiogram and a follow-up echocardiogram at 12 and/or 36 months. Data from 4 studies were included in the present analysis. LVM was normalized to height (in meters) to the 2.7 power (LVM/h = LVM/m(2.7)). RESULTS: In total, 45 adult patients (34 men and 11 women) with a confirmed diagnosis of Fabry disease and serial echocardiograms obtained at baseline and after 12 and/or 36 months of treatment were included. The mean (SD) age of this cohort was 39.8 (10.4) years (range, 18.9-67.2 years), and the mean weight was 72.5 (13.4) kg (range, 46.7-102.9 kg). Forty-two patients were white, 2 were Hispanic, and 1 was classified as other. At baseline, 14 patients had LVH (mean LVM/h = 55.4 [5.7] g/m(2.7)). After 12 months of ERT with agalsidase alfa, LVM/h decreased significantly by 9.2 (7.9) g/m(2.7) in 9 patients (P = 0.008), and after 36 months, LVM/h decreased significantly by 5.1 (7.5) g/m(2.7) in 10 patients (P = 0.037). In patients without baseline LVH (n = 31), a significant increase in LVM/h was observed after 12 months of treatment (3.6 [5.7] g/m(2.7); P = 0.002). After 36 months of treatment, however, there was no significant change from baseline in 10 patients (2.1 [7.9] g/m(2.7); P = NS). CONCLUSION: Treatment with agalsidase alfa for 12 or 36 months was associated with reduced LVM in these patients with Fabry disease with baseline LVH, and it appeared to stabilize LVM in these patients without baseline LVH.
BACKGROUND:Fabry disease is an X-linked disease caused by a deficiency in the activity of the lysosomal enzyme alpha-galactosidase A. Affected individuals typically develop left ventricular hypertrophy (LVH) among other pathologies. OBJECTIVE: The purpose of the present study was to investigate the effect of >or=12 months of enzyme replacement therapy (ERT) with agalsidase alfa on LV mass (LVM) in men and women with Fabry disease. METHODS: This was a retrospective, blinded, pooled analysis of data from several studies assessing the effect of ERT with agalsidase alfa on LVM in patients with Fabry disease with baseline LVH. Men and women aged >or=18 years with a confirmed diagnosis of Fabry disease who had received >or=36 months of ERT with agalsidase alfa were eligible, provided they had a baseline echocardiogram and a follow-up echocardiogram at 12 and/or 36 months. Data from 4 studies were included in the present analysis. LVM was normalized to height (in meters) to the 2.7 power (LVM/h = LVM/m(2.7)). RESULTS: In total, 45 adult patients (34 men and 11 women) with a confirmed diagnosis of Fabry disease and serial echocardiograms obtained at baseline and after 12 and/or 36 months of treatment were included. The mean (SD) age of this cohort was 39.8 (10.4) years (range, 18.9-67.2 years), and the mean weight was 72.5 (13.4) kg (range, 46.7-102.9 kg). Forty-two patients were white, 2 were Hispanic, and 1 was classified as other. At baseline, 14 patients had LVH (mean LVM/h = 55.4 [5.7] g/m(2.7)). After 12 months of ERT with agalsidase alfa, LVM/h decreased significantly by 9.2 (7.9) g/m(2.7) in 9 patients (P = 0.008), and after 36 months, LVM/h decreased significantly by 5.1 (7.5) g/m(2.7) in 10 patients (P = 0.037). In patients without baseline LVH (n = 31), a significant increase in LVM/h was observed after 12 months of treatment (3.6 [5.7] g/m(2.7); P = 0.002). After 36 months of treatment, however, there was no significant change from baseline in 10 patients (2.1 [7.9] g/m(2.7); P = NS). CONCLUSION: Treatment with agalsidase alfa for 12 or 36 months was associated with reduced LVM in these patients with Fabry disease with baseline LVH, and it appeared to stabilize LVM in these patients without baseline LVH.
Authors: Saskia M Rombach; Bouwien E Smid; Gabor E Linthorst; Marcel G W Dijkgraaf; Carla E M Hollak Journal: J Inherit Metab Dis Date: 2014-02-04 Impact factor: 4.982
Authors: Lubor Goláň; Ozlem Goker-Alpan; Myrl Holida; Ikka Kantola; Mariusz Klopotowski; Johanna Kuusisto; Aleš Linhart; Jacek Musial; Kathleen Nicholls; Derlis Gonzalez-Rodriguez; Reena Sharma; Bojan Vujkovac; Peter Chang; Anna Wijatyk Journal: Drug Des Devel Ther Date: 2015-07-08 Impact factor: 4.162
Authors: Derralynn A Hughes; Kathleen Nicholls; Suma P Shankar; Gere Sunder-Plassmann; David Koeller; Khan Nedd; Gerard Vockley; Takashi Hamazaki; Robin Lachmann; Toya Ohashi; Iacopo Olivotto; Norio Sakai; Patrick Deegan; David Dimmock; François Eyskens; Dominique P Germain; Ozlem Goker-Alpan; Eric Hachulla; Ana Jovanovic; Charles M Lourenco; Ichiei Narita; Mark Thomas; William R Wilcox; Daniel G Bichet; Raphael Schiffmann; Elizabeth Ludington; Christopher Viereck; John Kirk; Julie Yu; Franklin Johnson; Pol Boudes; Elfrida R Benjamin; David J Lockhart; Carrolee Barlow; Nina Skuban; Jeffrey P Castelli; Jay Barth; Ulla Feldt-Rasmussen Journal: J Med Genet Date: 2016-11-10 Impact factor: 6.318