HEREDITARY CERULOPLASMIN DEFICIENCY, DEMENTIA AND DIABETES-MELLITUS

We report two brothers with complete caeruloplasmin deficiency. The br others 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 linka ge between the deficiency and various polymorphic markers flanking the caeruloplasmin gene on chromosome 3q25. This is consistent with a mut ation of the caeruloplasmin gene. Caeruloplasmin catalyses the oxidati on of ferrous iron to ferric iron. Both brothers have low serum iron a nd increased liver iron. The index patient was given caeruloplasmin-co ntaining, fresh-frozen plasma. A dose of 2.6 mg caeruloplasmin increas ed serum iron from 5 mu M/l to 10 mu M/l. A dose of approximately 72 m g increased serum iron from 5 mu M/l to 19 mu M/l. The abnormal serum and liver iron levels, and the caeruloptasmin-induced rise in serum ir on, confirm a previous suggestion that caeruloplasmin maintains the no rmal rate of flow of iron from store to transferrin. Dementia and diab etes mellitus have been described in only one other homozygote. The ab sence of copper overload, and the linkage of the deficiency with chrom osome 3q25, distinguish this condition from Wilson's disease.