NBIA

Neurodegeneration with Brain Iron Accumulation (NBIA) encompasses a collection of disorders characterized by extrapyramidal symptoms and abnormal iron deposition in the deep basal ganglia. Aceruloplasminemia is an autosomal recessive disease caused by mutations in the ceruloplasmin gene.

Pathogenesis

Ceruloplasmin, synthesized in the liver, plays a crucial role not only in copper transport but also possesses ferrooxidase activity, which is responsible for oxidizing divalent iron (Fe2+) to trivalent iron (Fe3+). In aceruloplasminemia, the absence or malfunction of ceruloplasmin leads to iron deposition in the brain and liver due to impaired iron metabolism.

Clinical manifestations

Individuals with aceruloplasminemia often first develop diabetes mellitus in their 20s and 30s, a consequence of iron accumulation in the pancreas. Iron deposition in the retina can lead to retinitis pigmentosa, while deposition in the brain is typically associated with involuntary movements, cerebellar ataxia, extrapyramidal symptoms, and dementia, which tend to manifest in the 40s.

Characteristic blood tests for aceruloplasminemia include low ceruloplasmin levels, low copper levels, and high ferritin levels, reflecting the underlying disruptions in metal metabolism.

Radiographic features

On MRI, T1WI, T2WI, and FLAIR sequences show hypointensities in the basal ganglia, thalamus, dentate nucleus, substantia nigra, and red nucleus.