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Ceruloplasmin is a serum ferroxidase responsible for 95% copper transport in the blood. It is well known for its role in the pathogenesis of Wilson disease and regulating iron metabolism.[1] Also, ceruloplasmin is a positive acute-phase reactant, meaning its levels increase in inflammatory conditions or cell injury.[2] Copper is a trace element that acts as a cofactor for multiple enzymes in critical cellular reactions, such as cytochromes, which participate in the electron transport chain and redox catalysis.[3] Recent studies have shown that alterations of ceruloplasmin protein and copper homeostasis are associated with Alzheimer disease.[4][5]

Ceruloplasmin is undetectable before 20 weeks of gestation. Concentrations gradually rise to 25 to 40% of average adult concentrations and, by six months, are close to adult concentrations.[28] Special Situations There have been reports of inherited aceruloplasminemia in several families, and it is a genetic cause of ceruloplasmin deficiency; these patients have neurodegeneration and iron deposition in the brain.[29] Concerning aceruloplasminemia, a diagnosis of aceruloplasminemia could be suspected based upon a biochemical profile showing very low to absent ceruloplasmin in serum, high ferritin, low copper, low iron, microcytic anemia refractory to iron supplementation, and characteristic imaging features. Homozygous cases have distinctive imaging features with marked hypointensity of the liver, basal ganglia nuclei, thalami, dentate nuclei, and cerebral/cerebellar cortices on T2 MRI. MRI of heterozygous cases may reveal cerebellar atrophy without hypointensity of the basal ganglia.[30] Menkes disease is an X-linked recessive disorder caused by a mutation in the ATP7A protein. With this mutation, copper cannot be transported out of the GI tract; therefore, copper is unavailable to the liver, which causes low ceruloplasmin levels. The patients present in infancy have sparse, brittle, and kinky hair, growth retardation and neurologic degradation, and death if untreated in the first few years of life.[31]

Menkes disease is an X-linked recessive disorder caused by a mutation in the ATP7A protein. With this mutation, copper cannot be transported out of the GI tract; therefore, copper is unavailable to the liver, which causes low ceruloplasmin levels. The patients present in infancy have sparse, brittle, and kinky hair, growth retardation and neurologic degradation, and death if untreated in the first few years of life.[31] Wilson disease results from an autosomal recessive mutation in the ATP7B protein. Mutations in ATP7B (located on chromosome 13) lead to Wilson disease. ATP7B is an efflux transporter in the liver, but it is also essential in the Trans-Golgi Network for transferring copper for the metalation of ceruloplasmin and biliary copper excretion.[32] The point mutation H1069Q is the most common ATP7B mutation in patients from Central, Eastern, and Northern Europe, and 50 to 80% of Wilson disease patients from these countries carry at least one H1069Q allele.[33] Mutations resulting in completely absent or non-functional ATP7B protein activity are associated with early-onset, typically hepatic, severe Wilson disease; these mutations are comparatively rare.[34] It is characterized by hepatolenticular degeneration due to copper deposition in organs, including the basal ganglia, cornea, and liver. In Wilson's disease, ceruloplasmin levels are usually low, but urinary excretion of copper is high. Liver biopsy results show high copper content. Clinically, a dark ring around the iris suggests a diagnosis of Wilson disease. This sign is known as a Kayser-Fleischer ring.[35]