Increased plasma lipid peroxidation in patients with aceruloplasminemia.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism due to mutations in the ceruloplasmin gene. Although the presence of these mutations reveals an essential role for ceruloplasmin in human biology, the mechanisms of tissue injury in this disease are unknown. We report here on the identification of increased plasma lipid peroxidation in multiple affected family members with aceruloplasminemia. Consistent with the absence of serum ceruloplasmin, plasma ferroxidase activity was markedly reduced and serum ferritin was significantly increased. Plasma lipid peroxidation was determined as thiobarbituric acid-reactive products (TBA products) in plasma samples from control, heterozygote, and affected patients. Basal levels of lipid peroxides were three times control values in patients with aceruloplasminemia and were significantly increased in these patients in the presence of copper ions and hydrogen peroxide. In each case these increases were suppressed by the addition of exogenous ceruloplasmin. These data suggest that increased susceptibility to lipid peroxidation may contribute to the unique neuropathology observed in patients with aceruloplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia.