Aceruloplasminemia: an update.

Aceruloplasminemia is an inherited neurodegenerative disorder involving "neurodegeneration with brain iron accumulation," which is caused by genetic defects in the ceruloplasmin gene. Ceruloplasmin is a multicopper oxidase with ferroxidase activity that oxidizes ferrous iron following its transfer to extracellular transferrin. In the central nervous system, a glycosylphosphatidylinositol-linked ceruloplasmin bound to the cell membranes was found to be the major isoform of this protein. Aceruloplasminemia is characterized by diabetes, retinal degeneration, and progressive neurological symptoms, including extrapyramidal symptoms, ataxia, and dementia. Clinical and pathological studies and investigations of cell culture and murine models revealed that there is an iron-mediated cellular radical injury caused by a marked accumulation of iron in the affected parenchymal tissues. The aim of this chapter is to provide an overview of not only the clinical features, genetic and molecular pathogenesis, and treatment of aceruloplasminemia but also the biological and physiological features of iron metabolism.