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 represents a rare autosomal recessive disorder characterized by iron accumulation in multiple organs, particularly the brain, due to mutations in the ceruloplasmin gene.

Aceruloplasminemia results from biallelic mutations in the CP gene located on chromosome 3q23-q24, leading to complete absence or severe dysfunction of ceruloplasmin ferroxidase activity. Ceruloplasmin is a copper-containing α2-glycoprotein synthesized primarily in hepatocytes that carries more than 95% of plasma copper and serves as the principal ferroxidase enzyme responsible for converting ferrous iron (Fe²⁺) to ferric iron (Fe³⁺). This conversion is essential for iron binding to transferrin and subsequent transport throughout the circulation. 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.

Referenes

1. Grisoli, Marina, et al. "MR imaging of cerebral cortical involvement in aceruloplasminemia." American journal of neuroradiology 26.3 (2005): 657-661.