Hereditary aceruloplasminemia (OMIM #604290) is a rare autosomal recessive disorder due to mutations of Cp, the gene that encodes the copper-binding protein ceruloplasmin (Cp). The first report of hereditary aceruloplasminemia was published in 1987 in Japan. The patient was a 52-year-old woman who had a movement disorder that resembled Parkinson's disease, blepharospasm, retinal degeneration, and diabetes mellitus. Her serum immunofixation test revealed that her serum Cp concentration was very low. Computed tomography scanning revealed increased amounts of iron in her basal ganglia and liver. Subsequent histologic evaluation confirmed that there was increased iron in her basal ganglia and substantia nigra and in her liver, without increased copper.

The frequency of homozygosity for deleterious Cp mutations in non-consanguineous marriages in Japan was estimated to be 1 per 2,000,000 population. Aceruloplasminemia has been reported in several countries including Japan, China, Ireland, Belgium, France, Italy, and the US. More Japanese patients have been reported than any other nationality. Altogether, about 60 patients with hereditary aceruloplasminemia have been described.

Ceruloplasmin (Cp) biochemistry

Cp is a plasma metalloprotein, an alpha-2 glycoprotein polypeptide of 1046 amino acids. A member of the multi-copper oxidase enzyme family, Cp is the principal copper transport protein in plasma. Cp is synthesized in hepatocytes where it binds copper, and is thereafter secreted into plasma. About 95% of circulating plasma copper is bound to Cp; the remainder is bound to albumin, precuprein, and complexes of copper and amino acids. Each Cp molecule can bind and transport six atoms of copper.