Hereditary caeruloplasmin deficiency, dementia and diabetes mellitus

QJM. 1994 Nov;87(11):663-70.


We report two brothers with complete caeruloplasmin deficiency. The brothers presented with dementia and diabetes mellitus. Twelve relatives have partial caeruloplasmin deficiency. There is no copper overload. Transmission is autosomal recessive. DNA analysis showed genetic linkage between the deficiency and various polymorphic markers flanking the caeruloplasmin gene on chromosome 3q25. This is consistent with a mutation of the caeruloplasmin gene. Caeruloplasmin catalyses the oxidation of ferrous iron to ferric iron. Both brothers have low serum iron and increased liver iron. The index patient was given caeruloplasmin-containing, fresh-frozen plasma. A dose of 2.6 mg caeruloplasmin increased serum iron from 5 microM/l to 10 microM/l. A dose of approximately 72 mg increased serum iron from 5 microM/l to 19 microM/l. The abnormal serum and liver iron levels, and the caeruloplasmin-induced rise in serum iron, confirm a previous suggestion that caeruloplasmin maintains the normal rate of flow of iron from store to transferrin. Dementia and diabetes mellitus have been described in only one other homozygote. The absence of copper overload, and the linkage of the deficiency with chromosome 3q25, distinguish this condition from Wilson's disease.

MeSH terms

  • Brain / pathology
  • Ceruloplasmin / deficiency*
  • Ceruloplasmin / genetics
  • Dementia / genetics*
  • Dementia / pathology
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / pathology
  • Genes, Recessive
  • Homozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Pedigree


  • Ceruloplasmin