Wilson's disease (hepato-lenticular degeneration) is due to a deficiency of a substance called coeruloplasmin.

Coeruloplasmin carries copper in the blood. As a result, the level of copper cannot be maintained in the blood, excessive amounts are lost in the urine, and more important, are deposited in various organs, including the liver and the basal ganglia (lenticular nucleus). Several members of a family can be affected.

Severe involuntary movements develop in youth, and the patients become progressively more disabled, and deteriorate mentally. Later they develop liver failure.

Copper is also deposited in the corneas of the eyes, producing a golden brown ring -- the Kayser-Fleischer ring.

Wilson's disease is an autosomal recessive disease, with an incidence of about 1 in 30,000. The estimated heterozygous carrier rate is about 1 in 90, meaning that 1 in 90 people are unaffected carriers of this defective gene. The disease affects men and women equally and occurs in all races.

The Wilson's disease gene (WND) has been mapped to chromosome 13 (13q14.3) (2) and is expressed primarily in the liver, kidney, and placenta but has also been found in the heart, brain, and lung, albeit at much lower levels. The gene codes for a P-type adenosinetriphosphatase that transports copper into bile and incorporates it into ceruloplasmin.

The defect in the Wilson's disease gene causes impaired biliary excretion of copper (copper is mainly excreted through biliary excretion), leading to accumulation of copper in the body.

Copper deposition is said to cause tissue damage through the generation of free radicals, depletion of glutathione, and fatty oxidation. In the hepatocytes, it causes chronic hepatitis, fibrosis, and cirrhosis.

Once the liver's storage capacity for copper is exceeded, copper is released into the bloodstream and accumulates in the brain, joints, kidney, cornea, heart, and pancreas. Copper overload in the brain causes neuropsychiatric problems. Kayser-Fleischer rings result from copper deposition in Descemet's membrane of the cornea.

Clinical features
Clinical symptoms rarely develop before 5 years of age, despite the biochemical defect being present at birth. The average concentration of hepatic copper may reach 20 times normal levels, whilst plasma cerulopasmin levels are typically less than 30% of normal.

The age of presentation seems to correlate with the organ system involved. About half (40-50%) of patients first present with hepatic symptoms and half (40-50%) with neurologic symptoms. The average age for hepatic symptoms is 10 to 14 years, compared with 19 to 22 years for neurologic symptoms. Patients rarely present after age 40.

Clinical manifestations

Chronic active hepatitis
Fulminant liver failure 

Mood disorder
Cognitive impairment


Renal tubular acidosis

Kayser-Fleischer rings
Sunflower cataracts 


Treatment Treatment is aimed at reducing body stores of copper. A low-copper diet is started and chelating agents are given to help remove excess copper. Foods to avoid include shellfish, chocolate, nuts, and liver.

Penicillamine, trientine and zinc acetate have been approved for treatment of Wilson's Disease.

Liver transplantation is effective in patients with fulminant Wilson's disease that does not respond to the usual treatment. Because the primary defect resides within the liver, transplantation is curative and the outcome often is excellent.

I was told a story over the weekend that there was a young (20s) woman from Singapore who, after flying in to London one day got admitted to hospital for jaundice and generally feeling unwell. This came on acutely, over a period of one or two days. It turned out that she had fulminant hepatic failure and required a liver transplant! This was in a previously well lady who had never had any serious health problems prior to this incident.

Anyway, she was lucky that she was covered by insurance (from her employer, apparently) because there would have been no way she could have afforded to pay for a liver transplant at that point in time in a foreign land.

The liver transplant operation supposedly went well but she died some time after.

Moral of the story: what you don't know can bloody well kill you when you least expect it.

- http://www.postgradmed.com/issues/2000/02_00/morrison.htm
- the Merck Manual, 1999 Palm edition.

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