C Simoncini1, S Torri1, V Montano1, L Chico1, F Gruosso1, A Tuttolomondo2, A Pinto2, I Simonetta2, V Cianci3, A Salviati4, V Vicenzi5, G Marchi6, D Girelli6, D Concolino7, S Sestito7, M Zedde8, G Siciliano1, Michelangelo Mancuso9. 1. Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy. 2. Internal Medicine and Stroke Care Ward, Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (Promise) G. D'Alessandro, University of Palermo, Palermo, Italy. 3. Regional Epilepsy Centre, Great Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy. 4. Lab Functional Genomics, Department of Biotechnology, Univ Verona, Genartis srl, Verona, Italy. 5. Medical Genetics Unit, ASL 9, Verona, Italy. 6. Internal Medicine Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. 7. Department of Medical and Surgical Sciences, Pediatric Unit, "Magna Graecia" University, Catanzaro, Italy. 8. Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy. 9. Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy. michelangelo.mancuso@unipi.it.
Abstract
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. METHODS: We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. RESULTS: AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels. CONCLUSIONS: Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.
BACKGROUND:Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. METHODS: We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. RESULTS: AOPP levels were higher in patients than in controls (p < 0.00001) and patients presented decreased levels of antioxidant defences (FRAP and thiols) with respect to controls (p < 0.00001). In a small group of eight treatment-naïve subjects with FD-related mutations, we found altered levels of oxidative stress parameters and incipient signs of organ damage despite normal lyso-Gb3 levels. CONCLUSIONS: Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.
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