OBJECTIVE: Aceruloplasminemia is an iron metabolic disorder caused by mutations in the ceruloplasmin gene. It is characterized by progressive neurodegeneration in association with iron accumulation. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with the products of lipid peroxidation in the serum, cerebrospinal fluid, and brain tissues. To clarify the free radical-mediated tissue injury caused by intracellular iron accumulation through mitochondrial dysfunction. PATIENTS AND METHODS: We have measure brain oxygen and glucose metabolisms using positron emission tomography (PET) and examined brains at autopsy for iron contents and activities of the mitochondrial respiratory chain in two affected patients who had different truncation mutations of the ceruloplasmin gene. RESULTS: PET showed a marked decrease in glucose and oxygen consumption in the entire brain of aceruloplasminemia patients, with a preponderance of metabolic reduction in basal ganglia. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximately 45% and 42% respectively for complexes I and IV. An inverse relationship was shown between the amounts of iron accumulated and the levels of mitochondrial enzyme activities in all the brain regions examined. CONCLUSION: Iron-mediated free radicals may contribute to the impairment of mitochondrial energy metabolism in aceruloplasminemia.
OBJECTIVE:Aceruloplasminemia is an iron metabolic disorder caused by mutations in the ceruloplasmin gene. It is characterized by progressive neurodegeneration in association with iron accumulation. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with the products of lipid peroxidation in the serum, cerebrospinal fluid, and brain tissues. To clarify the free radical-mediated tissue injury caused by intracellular iron accumulation through mitochondrial dysfunction. PATIENTS AND METHODS: We have measure brain oxygen and glucose metabolisms using positron emission tomography (PET) and examined brains at autopsy for iron contents and activities of the mitochondrial respiratory chain in two affected patients who had different truncation mutations of the ceruloplasmin gene. RESULTS: PET showed a marked decrease in glucose and oxygen consumption in the entire brain of aceruloplasminemiapatients, with a preponderance of metabolic reduction in basal ganglia. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximately 45% and 42% respectively for complexes I and IV. An inverse relationship was shown between the amounts of iron accumulated and the levels of mitochondrial enzyme activities in all the brain regions examined. CONCLUSION:Iron-mediated free radicals may contribute to the impairment of mitochondrial energy metabolism in aceruloplasminemia.