FAMILIAL DEMENTIA DUE TO A FRAMESHIFT MUTATION IN THE CERULOPLASMIN GENE

Acaeruloplasminaemia is an autosomal recessive disorder affecting iron metabolism which results in diabetes, retinal degeneration and neurol ogical disease. We previously reported the clinical and laboratory fea tures of two brothers with absent serum caeruloplasmin and dementia. W e now demonstrate that these two patients have a novel mutation in the caeruloplasmin gene. Definitive demonstration of a caeruloplasmin gen e mutation in this family extends the clinical spectrum of this diseas e and suggests that acaeruloplasminaemia must be considered in the dia gnostic evaluation of the inherited dementias. Although the precise me chanisms leading to dementia in this disease are unknown, these data m ay have broad implications for our understanding of the role of iron- and oxidant-mediated tissue injury in a variety of human neurodegenera tive diseases.