Aceruloplasminemia

Abstract

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism characterized by diabetes, retinal degeneration, and neurologic symptoms. Affected patients evidence marked parenchymal iron accumulation in conjunction with an absence of circulating serum ceruloplasmin and molecular genetic analysis reveals inherited mutations in the ceruloplasmin gene. Taken together with earlier studies that characterized ceruloplasmin as a ferroxidase and recent work indicating an essential role for a homologous multicopper oxidase in iron metabolism in Saccharomyces cerevisiae, these findings reveal an essential role for ceruloplasmin in human iron metabolism. The presence of neurologic symptoms in patients with aceruloplasminemia is unique among the characterized disorders of iron metabolism, and recent findings indicate that astrocyte-specific ceruloplasmin gene expression is critical for iron metabolism and neuronal survival in the retina and basal ganglia. The discovery of this disease provides new insights into the pathways of CNS iron metabolism of direct relevance to a variety of nutritional and genetic disorders of childhood.