Alternative Names: Inherited Copper Toxicosis.

A genetic disorder called Wilson's disease affects copper metabolism and leads to low serum and hair copper levels but high levels in the liver and brain. This can be a serious and even fatal problem unless treated by chelating agents; BAL or penicillamine is most often used as it binds copper in the gut and carries it out. This is an inherited liver disorder named after British neurologist Samuel Wilson. The small intestine absorbs too much copper and the liver excretes too little of it, resulting in a copper buildup in the liver and brain.

The copper toxicosis of Wilson's disease is characterized, from birth on, by an average concentration of hepatic copper 20 times higher than normal and by deficiency of the plasma copper protein ceruloplasmin, averaging about 30% of normal. These concentrations are diagnostic of the disease, but they are present in every infant during the first 2-3 months of life, making diagnosis before 6 months of age unreliable. However, because clinical manifestations are never seen before the age of 5 years, studies to confirm or exclude the diagnosis in children at significant risk of Wilson's disease can be safely delayed until the second year of life.

In about 40 to 50% of patients, the first manifestations of disease occur in the liver. The initial illness may be an episode of acute hepatitis, occasionally misdiagnosed as infectious mononucleosis. Although the patient may be asymptomatic for years, hepatitis--acute, chronic active, or fulminant--may develop at any time. Whether or not such an illness occurs, hepatic pathology progresses to fibrosis and ultimately to cirrhosis.

Incidence

• An otherwise unexplained hepatic, neurologic, or psychiatric disease
• Otherwise unexplained persistent, asymptomatic transaminasemia
• A sibling, parent, or cousin with Wilson's disease
• When Wilson's disease is suspected, the diagnosis generally can be unequivocally confirmed if the patient has one of the following pairs of abnormalities:
  
  • Deficiency of oxidase-active ceruloplasmin (< 20 mg/dL) and excess of hepatic copper (> 250 ug/gm [> 3.9 umol/gm] dry liver) accompanied by histopathologic changes compatible with Wilson's disease;
  • Deficiency of ceruloplasmin and the presence of Kayser-Fleischer rings confirmed by an ophthalmologist using a slit lamp;
  • The confirmed presence of Kayser-Fleischer rings and motor neurologic abnormalities of the kind listed above;
  • Excess of hepatic copper and abnormally low incorporation of 64Cu into ceruloplasmin, despite a normal concentration of ceruloplasmin (20 to 30 mg/dL);
  • Deficiency of ceruloplasmin and urinary excretion of space (> 100 ug or 1.6 umol) copper in 24 hours, without administration of penicillamine.