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. Althoug h the presence of these mutations reveals an essential role for cerulo plasmin in human biology, the mechanisms of tissue injury in this dise ase are unknown. We report here on the identification of increased pla sma lipid peroxidation in multiple affected family members with acerul oplasminemia. Consistent with the absence of serum ceruloplasmin, plas ma ferroxidase activity was markedly reduced and serum ferritin was si gnificantly increased. Plasma lipid peroxidation was determined as thi obarbituric acid-reactive products (TBA products) in plasma samples fr om control, heterozygote, and affected patients. Basal levels of lipid peroxides were three times control values in patients with acerulopla sminemia and were significantly increased in these patients in the pre sence of copper ions and hydrogen peroxide. In each case these increas es were suppressed by the addition of exogenous ceruloplasmin. These d ata suggest that increased susceptibility to lipid peroxidation may co ntribute to the unique neuropathology observed in patients with acerul oplasminemia and imply a role for free radical-mediated tissue injury in degenerative disorders of the basal ganglia.