Abstract
Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a new disease characterized by systemic hemosiderosis, diabetes mellitus, neurological abnormalities and pigment degeneration of the retina. Loss of the ferroxidase activity of ceruloplasmin results in systemic iron deposition and tissue damage. Neuroimaging studies reveal iron deposition in basal ganglia and in the red and dentate nuclei. Cerebellar ataxia, extrapyramidal signs and dementia develop after middle age. We report a patient with undetectable serum ceruloplasmin levels and the above clinical manifestations. Sequence analysis of the cDNA of ceruloplasmin from this patient revealed an insertion of adenine in exon 3; this produced a premature stop codon.
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Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW (1993) The Wilson disease gene is a putative copper transporting Ptype ATPase similar to the Menkes gene. Nat Genet 5:327–337
Chelly J, Turner Z, Tonnesen T, Petterson A, Ishikawa-Brush Y, Tommerup N, Horn N, Monaco AP (1993) Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nat Genet 3:14–19
Goldstein IM, Kaplan HB, Edelson HS, Weissmann G (1979) Ceruloplasmin, a scavenger of superoxide anion radicals. J Biol Chem 254:4040–4045
Harris ZL, Takahashi Y, Miyajima H, Serizawa M, MacGillivray RTA, Gitlin JD (1995) Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci USA 92:2539–2543
Koschinsky ML, Funk WF, Oost BA van, MacGilivray RTA (1986) Complete cDNA sequence of human preceruloplasmin. Proc Natl Acad Sci USA 83:5086–5090
Logan JI, Harveyson KB, Wisdom GB, Hughes AE, Archbold GPR (1994) Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus. Q J Med 87:663–670
Mercer JFB, Livingston J, Ball B, Paynter JA, Begy B, Chandrasekharappa S, Lockhart P, Grimes A, Bhave M, Siemieniak D, Glover TW (1993) Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet 3:20–25
Miyajima H, Nishimura Y, Mizoguchi K, Sakamoto M, Shimizu T, Honda N (1987) Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration. Neurology 37:761–767
Morita H, Ikeda S, Yamamoto K, Morita S, Yoshida K, Nomoto S, Kata M, Yanagisawa N (1995) Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family. Ann Neurol 37:646–656
Osaki S, Johnson DA, Frieden E (1966) The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. J Biol Chem 241:2746–2751
Osaki S, Johnson DA, Frieden E (1971) The mobilization of iron from the perfused mammalian liver by a serum copper enzyme, ferroxidase I. J Biol Chem 246:3018–3023
Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chemov I, Devoto M, Brzustowicz LM, Cayanis E, Vitale E, Russo JJ, Matseoane D, Boukhgalter B, Wasco W, Figus AL, Loudianos J, Cao A, Sternlieb I, Evgrafov O, Parano E, Pavone L, Warburton D, Ott J, Penchaszadeh GK, Scheinberg IH, Gilliam TC (1993) Mapping, cloning and genetic characterization of the region containing the Wilson disease gene. Nat Genet 5:338–343
Samokyszyn VM, Reif DW, Miller DM, Aust SD (1991) Effects of ceruloplasmin on superoxide-dependent iron release from ferritin and lipid peroxidation. Free Radic Res Commun 12-13 153–159
Tanzi RE, Pertrukhin K, Pellequer JL, Wasco W, Ross B, Romano DM, Parano E, Pavone L, Brzustowica LM, Devoto M, Peppercorn J, Bush AI, Sternlieb I, Parastu M, Gusella JF, Evgrafov O, Penchaszadeh GK, Honic B, Edelman IS, Scares MB, Scheinberg IH, Gilliam TC (1993) The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 5:344–350
Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J (1993) Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet 3:7–13
Yoshida K, Furihata K, Takeda S, Nakamura A, Yamamoto K, Morita H, Hiyamuta S, Ikeda S, Shimizu N, Yanagisawa N (1995) A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 9: 267–272
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Okamoto, N., Wada, S., Oga, T. et al. Hereditary ceruloplasmin deficiency with hemosiderosis. Hum Genet 97, 755–758 (1996). https://doi.org/10.1007/BF02346185
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DOI: https://doi.org/10.1007/BF02346185