Wilson's Disease
Also known as hepatolenticular degeneration-an autosomal recessive disorder involving toxic levels of copper accumulation, predominantly in the liver and brain

Occurrence

• 1 in 20,000-40,000⁽¹⁾
• Majority of patients become symptomatic during teens, 2Os, or 30s^(1,2)

Presentation

• Hepatic: About one third of patients manifest liver disease, often fulminant hepatitis
• Neurologic: Early symptoms can include speech problems and motor abnormalities such as mild tremors, dystonia, ataxia, rigidity, and micrographia, which may progress to dysarthria and more severe motor deficits^(1,2)
• Psychiatric: Approximately one third of patients initially present with psychiatric abnormalities which may range from mild behavioral changes to symptoms almost impossible to distinguish from more severe disorders with associated psychosis and depression. Examples include depression, personality changes, and mood changes^(1,2)

Dangers of Misdiagnosis

• Symptoms often mistaken for other conditions: Delayed diagnosis increases potential for further damage

Diagnosis

• Kayser-Fleischer rings (slit-lamp exam)
• Serum ceruloplasmin levels
• 24-hour urine copper levels
• 64 Cu uptake levels
• Hepatic copper levels

Stages

• Presymptomatic: Copper silently accumulates in liver and brain
• Symptomatic: Copper toxicity manifested
• Recovery: Disease treated, resulting in partial or complete recovery from symptoms
• Maintenance: Stability achieved: GALZIN therapy maintains safe copper levels

GALZIN
A maintenance treatment for Wilson’s disease*
*After initial therapy with a chelating agent

• GALZIN is indicated for maintenance therapy in patients who have undergone initial treatment with a chelating agent
• GALZIN effectively controls copper levels in Wilson’s disease patients
• GALZIN has a different mechanism of action from chelating agents-it blocks absorption of copper from the intestine by binding copper to metallothionein in the lumen
• GALZlN is well-tolerated
  • Maintenance therapy, with an agent such as GALZIN, is
    essential for adequate control of copper levels; therefore,
    the physician must reinforce the need for strict compliance
    at each visit

Clinical experience with zinc acetate has been limited. The following adverse reactions have been reported in patients with Wilson’s disease on zinc therapy: gastric irritation, and elevations of serum alkaline phosphatase, amylase and lipase lasting frorn weeks to months The levels usually return to high normal within the first year or two of zinc therapy.

References
(1) Schilsky, ML. Wilson disease: Genetic basis of copper toxicity and natural history. Seminars in Liver Disease 1996;16:83-89.
(2) Brewer, GJ, Yuzabasiyan-Gurkan, V. Wilson disease. Medicine 1992;71(3):139-164.

Dosing

• The recommended dose of GALZIN for adults is 50 mg three times a day.
• In children 10 years of age or older, or in women who are pregnant, 25 mg t.i.d. is an effective dose, as long as the patient is compliant with therapy. The dose can be raised to 50 mg t.i.d. if monitoring indicates a lessening of control.
• GALZIN should be taken on an empty stomach, at least one hour before or two to three hours after meals.

Monitoring Copper Levels

• 24-hour urinary copper: The urinary excretion of copper is an accurate reflection of the body status of copper when patients are not on chelation therapy. Adequate zinc therapy will eventually decrease urinary copper excretion to 125 µg per 24 hours or less. A significant trend upward indicates impending loss of disease control.
• Non-ceruloplasmin-bound plasma copper
  (also known as free copper):
  This measurement is obtained by subtracting the ceruloplasmin-bound copper value from the total plasma copper value. Each mg of ceruloplasmin contains 3 µg of copper
• Oral 64 Cu: In adequately controlled patients, the radioactivity measured in plasma 1 or 2 hours after administration is less than 1.2% of the administered dose.
• Appropriate monitoring should also include:
  • clinical examination
  • serum biochemistries for liver function
  • follow-up slit-lamp examination
  • prothrombin time

Compliance

• While Wilson’s disease can occur anytime between the ages of 6 and 60, many patients become symptomatic during adolescence, their 2O's, or 30's. Patients should be reminded at every doctor’s visit of the need for strict compliance with the drug regimen because discontinuation of treatment leads to reemergence of symptoms.

For more information about Wilson’s disease, contact:
Wilson’s Disease Association, 4 Navaho Drive, Brookfield, CT 06804 Phone (800) 399-0266 http://www.wilsonsdisease.org