الفهرس 
GAUCHER DISEASEOnly 14 pages are availabe for public view
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Abstract
Abstract
Background: Enzymatic deficiency in Gaucher disease (GD) patients may induce a cascade of events that results in side effects, such as the production of reactive oxygen species (ROS) that can then generate the oxidative stress. Vitamin E is well accepted as nature’s most effective lipid-soluble and chain-breaking antioxidant. To our knowledge, no previous studies up till now have assessed the impact of vitamin E supplementation on disease severity among patients with GD. Objectives: This prospective clinical trial assessed the oxidant-antioxidant status in Egyptian patients with GD under enzyme replacement therapy (ERT) and its relation to disease severity. We also examined the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy in GD. Methods: Forty patients with GD with median age 10 years (11 had type 1 GD and 29 had type 3 GD) were enrolled. All patients were on stable dose of ERT. Patients were studied focusing on hepatic, skeletal, hematological and skeletal manifestations as well as history of splenectomy and ERT (dose, type and duration. Radiological examination included bone mineral density by DEXA scan, abdominal ultrasonography, Doppler echocardiography and transient elastography for assessment of liver stiffness. Severity score index (SSI) was assessed. Complete blood count, liver enzymes, lyso GL1, malondialdehyde (MDA) as an index for lipid peroxidation was measured and vitamin E levels as well as antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx] and peroxiredoxin 2 [PRDX2] levels) were assessed. Oxidant-antioxidant status was compared with levels of 40 age and sex-matched healthy controls. GD patients with vitamin E deficiency were randomized either to receive oral vitamin E or not. All patients were followed-up for 6 months and signs of any potential adverse effect were recorded. Results: All patients with GD had significantly higher levels of MDA and lower levels of vitamin E, GSH, SOD, GPX and PRDX2 compared with healthy controls (p<0.001 for all). Both patients groups with and without vitamin E supplementation were well-matched as regards baseline demographic, clinical, laboratory and radiological data. After 6 months of vitamin E supplementation, it was found that SSI, liver and spleen volumes were significantly lower post therapy (p<0.05). There was a trend towards lower liver stiffness post vitamin E supplementation; however, the difference was not statistically significant. ALT, lyso GL1 and MDA were significantly decreased post vitamin E therapy while vitamin E, GSH, SOD, GPX and PRDX2 were significantly higher post vitamin E therapy (p<0.05). Similar results were found when patients with and without vitamin E therapy were compered at study end. However, no significant difference was found as regards any of the studied variables at baseline and study end among GD patients without vitamin E supplementation. Baseline vitamin E was negatively correlated to SSI, lyso GL1 and MDA. There were significant negative correlations between PRDX2 and each of SSI, lyso GL1 and MDA while PRDX2 was positively correlated to vitamin E. Conclusions: Oxidative stress is prevalent in pediatric patients with GD and related to disease severity. Vitamin E supplementation for 6 months to pediatric patients with GD represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress and normalized the altered levels of antioxidant enzymes including PRDX2. Further longer studies including larger number of GD patients and higher doses of vitamin E according to the degree of vitamin E deficiency are needed to verify our results and test the long term effects of vitamin E among GD patients.