Wilson’s disease- what causes it?

While watching an episode of House , a psychotic patient was admitted into his ‘care’. After various complications and dead-end diagnoses, the patient in question was eventually found to have Wilson’s disease; a rare autosomal recessive genetic disorder which results in an accumulation of copper in the body tissues. Autosomal  means any chromosome other than the sex chromosomes.

http://brickswithoutclay.tumblr.com/post/1269915498/lucy-palmeiro-patient-6-the-socratic-method 

Due to this piling up of copper, suffers will experience neurological symptoms, liver disease and other intriguing consequences.

This disease stems from a mutation in a gene ATP7B. Since the gene is recessive, if both parents (the mutation is prevalent in 1% of people) have this gene, the child may develop Wilson’s disease.

Copper is essential for the body for a variety of functions, but predominantly acts as a cofactor for various enzymes. A cofactor is a non protein compound which must be present for enzyme controlled reactions to occur.

Usually, once copper ions enter the body via the intestines, copper is transferred inside bowel cells by a transporter protein on the plasma membrane, appropriately named copper membrane transporter 1 (CMT1) .

Inside these bowel cells, copper is bound to a protein called metallothionein and some is transported to an organelle known as the Golgi apparatus. The Golgi apparatus packages the copper into vesicles, and an enzyme (ATP7A) deposits this copper into the hepatic portal vein, a vessel carrying blood from the digestive system to the liver. Liver cells also contain the CMT1 protein, metallothionein (binding to copper to essentially store it) among other things. However they also comprise the ATP7A enzyme which binds copper to ceruloplasmin- the main copper carrying protein in the blood, thus this is the mechanism in which excess copper is removed.

The enzyme that both releases copper into the hepatic portal vein and into the blood stream bound to ceruloplasmin is impaired in a suffer of Wilson’s disease. This results in a large accumulation of copper in tissues.

In the liver, when there is surplus copper, oxidation will occur as copper oxidises components of the cells. In the liver, this leads to cirrhosis-scarring of the liver (why in this episode of house, one initial prognosis was alcoholism), fibrosis and chronic active hepatitis.

In the brain, copper is mainly deposited in the basal ganglia. This structure is mainly known for releasing neurotransmitters such as dopamine, which in turn plays a role in mood regulation, processing of stimuli and other functions. Thus, damage to this structure leads to psychiatric symptoms as seen on house. 

Nearing the end of this episode, the team investigate the patient’s eye to conclusively confirm Wilson’s disease. Excess copper builds up as an orange ring around the cornea, known as Kayser–Fleischer rings, which is what the team find.

There are many other symptoms of this disease, but I feel these are the most engaging to consider.

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