Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy |
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Authors: | Mariëlle J van BreemenSaskia M Rombach Nick DekkerBen J Poorthuis Gabor E LinthorstAeilko H Zwinderman Frank BreunigChristoph Wanner Johannes M Aerts Carla E Hollak |
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Institution: | a Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlandsb Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlandsc Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlandsd Department of Internal Medicine/Nephrology, Universitätsklinikum, Würzburg, Germany |
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Abstract: | Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2 mg/kg, agalsidase beta at 0.2 mg/kg or at 1.0 mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P = 0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients. |
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Keywords: | eNOS endothelial nitric oxide synthase ERT enzyme replacement therapy Gb2 galabiosylceramide Gb3 globotriaosylceramide GLA gene α-galactosidase A gene LVH left ventricular hypertrophy lysoGb3 globotriaosylsphingosine OPA o-phtaldialdehyde |
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