Aceruloplasminemia

Abstract

In 1987, Miyajima et al. [ [1] Miyajima H. Nishimura Y. Mizoguchi K. et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration. Neurology. 1987; 37: 761-767 Crossref PubMed Google Scholar ] first described a 52-year-old woman suffering from blepharospasm, retinal degeneration, diabetes mellitus, and neurodegeneration. Her symptoms were associated with an absence of circulating serum ceruloplasmin, elevated serum ferritin, a mild anemia, low serum iron, profound hepatic iron overload, and T2-weighted magnetic resonance images of her brain revealing iron overload specific to the basal ganglia and substantia nigra. A mutation was identified in her ceruloplasmin gene [ [2] Harris Z.L. Takahashi Y. Miyajima H. et al. Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 2539-2543 Crossref PubMed Scopus (508) Google Scholar ]. Originally diagnosed as suffering from “atypical Wilson disease”, the constellation of her findings suggested a novel disorder of iron metabolism associated with a lack of the copper-containing protein, ceruloplasmin. Termed ‘aceruloplasminemia’, this adult-onset, autosomal recessive disorder has now been associated with multiple distinct mutations in the ceruloplasmin gene [ 3 Yoshida K. Furihata K. Takeda S. et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat. Genet. 1995; 9: 267-272 Crossref PubMed Scopus (421) Google Scholar , 4 Daimon M. Kato T. Kawanami T. Tominaga M. et al. A nonsense mutation of the ceruloplasmin gene in hereditary ceruloplasmin deficiency with diabetes mellitus. Biochem. Biophys. Res. Commun. 1995; 217: 89-95 Crossref PubMed Scopus (49) Google Scholar , 5 Harris Z.L. Migas M.D. Hughes A.E. et al. Familial dementia due to a frameshift mutation in the ceruloplasmin gene. Q. J. Med. 1996; 89: 355-359 Crossref Scopus (39) Google Scholar , 6 Okamoto N. Wada S. Oga T. Kawabata Y. et al. Hereditary ceruloplasmin deficiency with hemosiderosis. Hum. Genet. 1996; 97: 755-778 Crossref PubMed Scopus (95) Google Scholar , 7 Hellman N.E. Kono S. Miyajima H. Gitlin J.D. Biochemical analysis of a missense mutation in aceruloplasminemia. J. Biol. Chem. 2002; 277: 1375-1380 Crossref PubMed Scopus (75) Google Scholar ].