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 non-
ceruloplasmin 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.