Erythrocyte Metabolism and Antioxidant Status of Patients with Wilson Disease with Hemolytic Anemia

Abstract

ABSTRACT:Wilson disease (WD) is an autosomal recessive disorder due to the defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain, kidneys, and cornea. Strikingly, the total serum copper concentration is always low in WD, even though the nonceruloplasmin copper level is still expected to be high. To assess the role of free radical reactions catalyzed by non-ceruloplasmin copper, we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on D-penicillamine therapy and eight healthy, age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. There was marked inhibition in erythrocyte enzymes, namely, hexokinase, total adenosine triphosphatase (ATPase), and glucose-6-phosphate dehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children, indicating altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be compromised as is evident from decreased glutathione (GSH) levels, decreased antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), increased lipid peroxidation, and deranged plasma antioxidants. Uric acid showed maximum decrease followed by ascorbic acid. These findings suggest that the free radical production by elevated non-ceruloplasmin copper through transition metal catalyzed reactions leads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia. (Pediatr Res 59: 593-597, 2006)

Sequence variation database for the Wilson disease copper transporter,ATP7B

“…Psychiatric disorders, kidney disease, and hemolysis can also be manifestations of WND. Presentation as hemolytic anemia, an infrequent mode of first presentation that is easily missed, results from oxidative stress associated with increased nonceruloplasmin copper in blood [Attri et al, 2006]. The onset of disease symptoms can occur as early as 3 years of age [Wilson et al, 2000], and has been reported into the seventh decade [Ala et al, 2005;Schilsky, 2005].…”

A Study of Distribution and Prevalence of Anaemia in School Going Children of Ghaziabad

“…[18] Other than iron other nutrients such as vitamin C, B12 and folic acid are involved in the formation of RBC. [19] Hence, decreased availability of any of these nutrients can produce anaemia. Low socioeconomic status and lack of health education of people is the main cause of high prevalence of anaemia in our country.…”

Zinc/copper ratio: a predictor of pancreatic function in chronic pancreatitis?

“…It is well established that copper can serve as a pro-oxidant by catalyzing the production of hydroxyl radical via Fenton reaction. It was suggested that copper ions bind to sulfhydryl groups in cells and inactivate the action of glucose-6-phosphate dehydrogenase and glutathione reductase, both of which are necessary for the reduction of oxidized glutathione to the reduced form of glutathione 26 . These effects would tend to decrease the reduced glutathione content of erythrocytes and make them more vulnerable to the oxidative effects of copper.…”