Familial dementia due to a frameshift mutation in the caeruloplasmin gene

Acaeruloplasminaemia is an autosomal recessive disorder affecting iron metabolism which results in diabetes, retinal degeneration and neurological disease. We previously reported the clinical and laboratory features of two brothers with absent serum caeruloplasmin and dementia. We now demonstrate that these two patients have a novel mutation in the caeruloplasmin gene. Definitive demonstration of a caeruloplasmin gene mutation in this family extends the clinical spectrum of this disease and suggests that acaeruloplasminaemia must be considered in the diagnostic evaluation of the inherited dementias. Although the precise mechanisms leading to dementia in this disease are unknown, these data may have broad implications for our understanding of the role of iron- and oxidant-mediated tissue injury in a variety of human neurodegenerative diseases.