Background &Aims: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulati...Background &Aims: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulation in the liver and brain. Methods: We herein studied a novel clinical type of aceruloplasminemia in which a low amount of ceruloplasmin was detected in the serum of a patient. The patient presented with an asymptomatic hepatic iron overload, retinal degeneration, and diabetes mellitus. Magnetic resonance imaging of the liver and basal ganglia showed T2-hypointensity signals associated with parenchy-mal iron accumulation because of an absence of the ferroxidase activity in ceruloplasmin. Results: A gene analysis showed a novel G969S mutation in the ceruloplasmin gene. A biochemical analysis of the patients’serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity. Conclusions: This novel clinical type of aceruloplasminemia should therefore be considered in the differential diagnosis of unexplained hemochromatosis, which is associated with a decrease in the serum ceruloplasmin level.展开更多
文摘Background &Aims: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulation in the liver and brain. Methods: We herein studied a novel clinical type of aceruloplasminemia in which a low amount of ceruloplasmin was detected in the serum of a patient. The patient presented with an asymptomatic hepatic iron overload, retinal degeneration, and diabetes mellitus. Magnetic resonance imaging of the liver and basal ganglia showed T2-hypointensity signals associated with parenchy-mal iron accumulation because of an absence of the ferroxidase activity in ceruloplasmin. Results: A gene analysis showed a novel G969S mutation in the ceruloplasmin gene. A biochemical analysis of the patients’serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity. Conclusions: This novel clinical type of aceruloplasminemia should therefore be considered in the differential diagnosis of unexplained hemochromatosis, which is associated with a decrease in the serum ceruloplasmin level.
