Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, resulting in impaired biliary copper excretion and toxic copper accumulation in tissues.

Pathophysiology

• Basic defect: Decreased biliary copper excretion due to defective ATP7B protein
• Mechanism: Impaired incorporation of copper into ceruloplasmin and reduced copper transport into bile
• Result: Copper accumulation in liver, brain, cornea, and other organs

Clinical Manifestations

Hepatic (Most common initial presentation)

• Acute hepatitis
• Chronic hepatitis
• Cirrhosis
• Fulminant hepatic failure

Neurological

• Movement disorders (tremor, dystonia, chorea)
• Psychiatric symptoms (depression, psychosis, behavioral changes)
• Dysarthria and dysphagia
• Cognitive impairment

Ophthalmologic

• Kayser-Fleischer rings (pathognomonic copper deposits in Descemet's membrane)
• Sunflower cataracts

Other Features

• Renal tubular acidosis
• Hemolytic anemia
• Arthritis
• Cardiomyopathy (rare)

Diagnostic Workup

• Serum ceruloplasmin: Usually decreased (<20 mg/dL)
• 24-hour urine copper: Elevated (>100 μg/24h)
• Hepatic copper content: Gold standard (>250 μg/g dry weight)
• Ophthalmologic examination: Slit-lamp for Kayser-Fleischer rings
• Genetic testing: ATP7B gene mutations
• Brain MRI: "Face of giant panda" sign in severe cases

Treatment

Chelation Therapy

• D-penicillamine: First-line, may worsen neurological symptoms initially
• Trientine: Alternative chelator, better tolerated neurologically
• Tetrathiomolybdate: For neurological presentations

Zinc Therapy

• Zinc acetate/sulfate: Blocks copper absorption, maintenance therapy
• Preferred for asymptomatic patients and maintenance