- Wilson is a rare hereditary disease caused by impaired biliary excretion of copper, resulting in progressive copper accumulation in particular body tissues.
|Normal Copper Homeostasis|
- The liver normally packages copper absorbed by the alimentary tract on the plasma protein "Ceruloplasmin" for transport to peripheral tissue. When there is excess copper, hepatocytes take in copper-loaded ceruloplasmin from the plasma and excrete the copper into the bile using the membrane transporter ATP7B. Thus, excess copper is cleared from the body with biliary excretion.
- Patients with Wilson Disease have a mutation in the ATP7B transporter and are not capable of biliary excretion of excess copper. Copper first builds up in the liver but eventually spills out into the plasma in free form, independently of ceruloplasmin. Free copper then deposits in a number of tissues and induces free radical cell injury by generating free radicals or inappropriately displacing other enzymatically important metals.
|Morphology and Clinical Consequences|
- The pathology of Wilson disease is characterized by free copper deposition in multiple organs which results in their dysfunction. Clinical manifestations are extremely variable and can manifest at any age.
- Copper accumulates especially in the basal ganglia with a preference for the putamen. A variety of neurological and psychiatric deficits may occur, including psychosis and a Parkinsons-like syndrome.
- A visibly brownish ring of copper deposition around the cornea is generally visible in those with neurological involvement. These "Kayser-Fleischer Rings" are virtually pathognomonic of Wilsons Disease.
- Urine Copper: Is highly elevated due to the extremely high plasma concentration of free, unbound copper in the plasma. Serum Ceruloplasmin: Is actually reduced in many patients with Wilson Disease, thus exacerbating the amount of free, unbound plasma copper.