Wilson's Disease Diagnosis and Management

Introduction to Wilson's Disease

Wilson's disease is an inherited autosomal recessive disorder caused by mutations in the ATP7B gene on chromosome 13, resulting in defective biliary excretion of copper and its toxic accumulation primarily in the liver and brain 1, 2
The disease results from mutations in the ATP7B gene, which encodes a copper-transporting P-type ATPase responsible for copper excretion into bile and incorporation into ceruloplasmin 1, 2, 3
More than 500 distinct mutations have been described, with approximately 380 confirmed to cause disease 1, 2
The gene frequency is 1 in 90-150, with disease incidence as high as 1 in 30,000 1, 2

Wilson's disease can present at any age from 3 years to the eighth decade, though most patients present between ages 5 and 35 1, 2, 5
Kayser-Fleischer rings (golden-brownish pigment deposits in Descemet's membrane at the corneal limbus) are present in 90% of patients with neurological manifestations but only 50-62% with primarily hepatic disease 1, 2, 5
Serum ceruloplasmin <20 mg/dL (though 18% of non-fulminant patients may have normal levels) 1, 2
Hepatic copper concentration >250 μg/g dry weight provides critical diagnostic information 7
24-hour urinary copper excretion (normal <40-50 μg/24h; in fulminant failure: 844-9375 μg/24h) 7

Treatment has two objectives: minimize dietary copper intake to <1-2 mg/day and promote excretion/detoxification of excess tissue copper through chelation therapy 1, 2
First-line treatment for symptomatic patients is copper chelation with D-penicillamine, though trientine and zinc acetate are alternatives 6
Without treatment, Wilson's disease is uniformly fatal 6
With appropriate treatment, life is prolonged and clinical improvement occurs in most patients 6