Aceruloplasminemia, an iron metabolic disorder.

Abstract

Aceruloplasminemia is an inherited disorder of iron metabolism caused by the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. It is characterized by iron accumulation in the brain as well as visceral organs. Clinically, the disease consists of the triad of adult-onset neurologic disease, retinal degeneration and diabetes mellitus. The neurological symptoms, which include involuntary movements, ataxia, and dementia, reflect the sites of iron deposition. Severe iron overload and extensive neuronal loss were observed in the basal ganglia, while iron deposition and neuronal cell loss were trivial in the frontal cortices. The cerebellar cortex showed marked loss of Purkinje cells. Iron deposition was more prominent in the astrocytes than in the neurons. Excess iron functions as a potent catalyst of biologic oxidation. Astrocytic deformity and globular structures are characteristic features in aceruloplasminemia brains. The globular structures in the astrocytes were seen in proportion to the degree of iron deposition and reacted positively to anti-4-hydroxynonenal, one of the indicators of lipid peroxidation, and anti-ubiquitin antibodies, but not to anti-alpha-synuclein antibody. The lack of ceruloplasmin may primarily damage astrocytes in the aceruloplasminemia brains through lipid peroxidation. Ceruloplasmin may play an essential role in neuronal survival in the central nervous system.