Oxidative Stress Status in Gaucher Disease under Enzyme Replacement Therapy

Abstract Background Enzymatic deficiency in patients with Gaucher disease (GD) may induce a cascade of events that results in production of reactive oxygen species that can then generate oxidative stress. Objectives This study assessed the oxidant-antioxidant status in Egyptian patients with GD under enzyme replacement therapy (ERT) and its relation to disease severity. Methods This study included 40 patients with GD with median age 10 years (11 had type 1 GD and 29 had type 3 GD). All patients were on stable dose of enzyme replacement therapy (ERT). All included patients were subjected to detailed medical history with special emphasis on hepatic, skeletal, hematological and skeletal manifestations as well as history of splenectomy and ERT (dose, type and duration. Abdominal ultrasonography was performed. Severity score index was assessed. Complete blood count, liver enzymes, lyso GL1, malondialdehyde (MDA) as an index for lipid peroxidation was measured and 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. Results Patients with GD had significantly higher levels of MDA compared with healthy controls (median, 19.6 versus 7.19 mg/dL; p < 0.001). GSH was significantly lower in GD patients with a median 0.95 versus healthy controls 8.92 mg/dL (p < 0.001). Mean levels of SOD, GPX and PRDX2 were significantly decreased in GD patients (p < 0.001 for all). Severity score index was positively correlated to MDA (r = - 0.511, p = 0.023) while negatively correlated to PRDX2 (r = - 0.562, p = 0.01). PRDX2 was negatively correlated to lyso GL1 (r = -0.569, p = 0.009). Conclusions Oxidative stress is prevalent in pediatric patients with GD and related to disease severity. This helps to understand GD pathophysiology ad allow the use of antioxidants as an adjuvant therapy to decrease disease burden.