Ceruloplasmin - Pathology

Pathology

Like any other plasma protein, levels drop in patients with hepatic disease due to reduced synthesizing capabilities.

Mechanisms of low ceruplasmin levels:

• Gene expression genetically low (aceruloplasminemia)
• Copper levels are low in general
  • Malnutrition/trace metal deficiency in the food source
• Copper does not cross the intestinal barrier due to ATP7A deficiency (Menkes disease)
• Delivery of copper into the lumen of the ER-Golgi network is absent in hepatocytes due to absent ATP7B (Wilson's disease)

Copper availability doesn't affect the translation of the nascent protein. However, the apoenzyme without copper is unstable. Apoceruloplasmin is largely degraded intracellularly in the hepatocyte and the small amount that is released has a short circulation half life of 5 hours as compared to the 5.5 days for the holo-ceruloplasmin.

Mutations in the ceruloplasmin gene (CP), which are very rare, can lead to the genetic disease aceruloplasminemia, characterized by hyperferritinemia with iron overload. In the brain, this iron overload may lead to characteristic neurologic signs and symptoms, such as cerebellar ataxia, progressive dementia, and extrapyramidal signs. Excess iron may also deposit in the liver, pancreas, and retina, leading to cirrhosis, endocrine abnormalities, and loss of vision, respectively.