Aceruloplasminemia: A genetic disorder in which there is absence of the protein ceruloplasmin from blood and accumulation of iron in the pancreas, liver and brain, causing diabetes and progressive neurodegeneration with the tremors and gait abnormalities characteristic of Parkinson disease.
Ceruloplasmin normally removes iron from cells. The absence of ceruloplasmin leads to the abnormal deposition of iron in cells, including those of the pancreas, liver, retina and the basal ganglia region of the brain. The iron deposition damages these tissues and leads to the clinical features of the disease which usually appear between 30 and 50 years of age.
In a typical case, a man in his 40s had a recent history of excessive thirst and urination (due to diabetes) and of progressive confusion. Treatment of the diabetes was begun. One day he suddenly left work and was found at home the next day sitting in a chair with the appearance of not having been to bed. When asked why he was not at work he replied, "What work?" Dementia progressed thereafter.
Aggressive treatment with deferoxamine, a chelating agent that takes up iron, may halt the progression of these complications.
Aceruloplasminemia is caused by mutations in the gene encoding ceruloplasmin on chromosome 3q. The gene is located in bands 3q23-q25.
Aceruloplasminemia is inherited as an autosomal recessive condition. Men and women with the disease have a pair of mutant ceruloplasmin genes, one from each of their parents.
Ceruloplasmin is an essential ferroxidase, an enzyme which catalyzes the oxidation of ferrous iron to ferric iron. This disease reveals the critical role of a copper-containing protein in iron trafficking. In aceruloplasminemia, the balance between the compartmentalization and storage of iron and the mobilization and transport of iron is disrupted.