About Wilson's Disease
Wilson's disease is an autosomal inherited metabolic defect caused by mutations in the ATP7B gene. ATP protein deficiency impairs biliary copper excretion, resulting in hepatic copper accumulation and copper toxicity. Serum copper levels tend to be lower than normal due to low levels of the plasma protein ceruloplasmin, which normally binds > 90% of serum copper. Non-ceruloplasmin serum copper ("free copper") levels increase as the disease progresses, leading to copper accumulation in other parts of the body and increased manifestation of psychiatric and neurologic symptoms over time.1
Clinical manifestations primarily involve the liver and brain
Wilson's disease may first present as hepatic disease or cirrhosis. This generally occurs in patients from the mid-to-late teens. Neurological symptoms typically appear in the early 20s, although age of onset extends from the teens to the 40s. The three major neurological symptoms -- dystonia, incoordination, and tremor -- closely resemble Parkinson's disease. About half of patients with neurological manifestations exhibit psychiatric symptoms.1
Ophthalmologic hallmark of Wilson's disease: Kayser-Fleischer rings
The Kayser-Fleischer ring is a copper deposit on the outer rim of the cornea. It is the most important diagnostic sign for identifying a patient with Wilson's disease and can only be diagnosed definitively using a slit lamp. The ring is found in 99% of such patients, with virtually all of these having neurological and psychiatric symptoms.1 The density of the ring correlates with the severity of the disease.2
A treatable disorder
Untreated Wilson's disease is a progressive and ultimately fatal condition.3 Before treatment was available, the average age of death was 30.6 years.4 But patients now benefit from chelation therapy, the mainstay of treatment today. It has proved highly effective. With the use of chelating agents, liver function usually improves in about a year, while neurologic and psychiatric symptoms usually improve between 6 and 24 months after initiating therapy. Wilson's disease requires lifelong treatment.1
Diagnosis: Tests for Wilson's Disease
| Test | Presentation in Wilson's disease | Reference range |
|---|---|---|
| Serum ceruloplasmin | Low in 85% of patients | 18 to 35 mg/dL |
| 24-hour urine copper levels | >100 µg in symptomatic patients; 60 to 100 µg in presymptomatic patients | 20-50 µg |
| Liver copper levels (based on liver biopsy) | > 200 µg dry weight of liver | 20 to 50 µg dry weight of liver |
| Kayser-Fleischer rings | Present in 99% of patients with neurologic and psychiatric symptoms; present in 30-50% of presymptomatic patients | Exist very rarely in individuals who do not have Wilson's disease |
Adapted from Brewer GJ. Wilson's disease. In: Kasper DL, Fauci AS, Longo DL, eds. Harrison's Principles of Internal Medicine. New York. 16th ed. McGraw-Hill. 2005:2313-15.
Important Safety Information
SYPRINE® is contraindicated in hypersensitive patients. Patients should be observed closely for signs of possible hypersensitivity. Patients receiving SYPRINE should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia. SYPRINE must be taken on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed. For the first month of treatment, the patient should have his temperature taken nightly, and report any symptom such as fever or skin eruption. The following adverse reactions have been reported from a clinical study: iron deficiency and systemic lupus erythematosus. You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
Reference: 1. Brewer GJ. Wilson's disease. In: Kasper DL, Fauci AS, Longo DL, eds. Harrison's Principles of Internal Medicine. New York. 16th ed. McGraw-Hill. 2005:2313-15. 2. Sullivan CA, Chopdar A, Shun Shin GA. Letters. Dense Kayser-Fleischer ring in a asymptomatic Wilson's disease (hepatolenticular degeneration). Br J Ophthalmol. 2002;86:114-23. 3. Parkes D. Wilson's disease. British Med J. 1984;288:1180-81. 4. Park DHR, McCabe P, Fell GS, Russell RI. Wilson's disease in Scotland. Gut. 1991;32:1541-45.
