Wilson's disease (hepatolenticular degeneration) occurs in individuals who have inherited an autosomal recessive defect that leads to an accumulation of copper far in excess of metabolic requirements. The excess copper is deposited in several organs and tissues, and eventually produces pathological effects primarily in the liver, where damage progresses to postnecrotic cirrhosis, and in the brain, where degeneration is widespread. Copper is also deposited as characteristic, asymptomatic, golden-brown Kayser-Fleischer rings in the corneas of all patients with cerebral symptomatology and some patients who are either asymptomatic or manifest only hepatic symptomatology.

Two types of patients require treatment for Wilson's disease: (1) the symptomatic, and (2) the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated.

The diagnosis, if suspected on the basis of family or individual history or physical examination, can be confirmed if the plasma copper-protein ceruloplasmin1 is < 20 mg/dL and either a quantitative determination in a liver biopsy specimen shows an abnormally high concentration of copper (> 250 mcg/g dry weight) or Kayser-Fleischer rings are present. Treatment has two objectives:

(1) to minimize dietary intake of copper;

(2) to promote excretion and complex formation (i.e., detoxification) of excess tissue copper.

The first objective is attained by a daily diet that contains no more than 1 or 2 mg of copper. Such a diet should exclude, most importantly, chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and cereals and dietary supplements enriched with copper, and be composed to as great an extent as possible of foods with a low copper content. Distilled or demineralized water should be used if the patient's drinking water contains more than 0.1 mg/L of copper.

For the second objective, a copper chelating agent is used.

In symptomatic patients, this treatment usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances.

Clinical experience to date suggests that life is prolonged with the above regimen.

Noticeable improvement may not occur for 1 to 3 months. Occasionally, neurologic symptoms become worse during initiation of therapy with penicillamine capsules. Despite this, the drug should not be withdrawn. Temporary interruption carries an increased risk of developing a sensitivity reaction upon resumption of therapy, although it may result in clinical improvement of neurological symptoms (see WARNINGS). If the neurological symptoms and signs continue to worsen for a month after the initiation of penicillamine capsules therapy, several short courses of treatment with 2,3 - dimercaprol (BAL) while continuing penicillamine capsules may be considered.

Treatment of asymptomatic patients has been carried out for over 30 years. Symptoms and signs of the disease appear to be prevented indefinitely if daily treatment with penicillamine capsules is continued.

* * *

1
    For quantitative test for serum ceruloplasmin see: Morell, A.G.; Windsor, J.; Sternlieb, I.; Scheinberg, I.H.: Measurement of the concentration of ceruloplasmin in serum by determination of its oxidase activity, in "Laboratory Diagnosis of Liver Disease", F.W. Sunderman; F.W. Sunderman, Jr. (eds.), St. Louis, Warren H. Green, Inc., 1968, pp. 193-195.