DESCRIPTION

Wilson disease (WD), or hepatolenticular degeneration, is a rare autosomal recessive disease of copper (Cu; Latin cuprum) metabolism with variable clinical presentation requiring high index of suspicion. WD can manifest as acute or chronic liver disease, fulminant liver failure with hemolytic crisis, or neuropsychiatric disorder, or it can be silent such as seen in asymptomatic siblings of person with WD.

EPIDEMIOLOGY

• Prevalence ranges from 1:30,000 to 1:67,000.
• WD should be considered in any individual between the ages of 3 and 55 years with liver abnormalities of uncertain cause.
  • Children are more likely to present with hepatic symptoms, whereas neurologic symptoms may be more common in young adults.
  • Women are more often seen to have liver disease, whereas men are more often to have neuropsychiatric symptoms.

RISK FACTORS

PATHOPHYSIOLOGY

• Cu is an essential metal to many proteins. The recommended intake is 0.9 mg/24 h, and the average Western diet provides 2 to 5 mg/24 h of Cu.
• Cu is absorbed by the enterocytes mainly in the duodenum and proximal small intestine and transported in the portal circulation in association with albumin and the amino acid histidine to the liver, where it is avidly removed from the circulation.
• The liver uses some Cu for metabolic needs, synthesizes and secretes the Cu-containing protein ceruloplasmin, and excretes excess Cu into the bile.
• Loss of ATP7B function causes (i) impaired biliary Cu excretion (resulting in toxic hepatocellular Cu accumulation and eventually exceeding liver storage capacity leading to deposition of Cu in brain, kidneys, cornea, pancreas etc.) and (ii) failure to incorporate Cu to ceruloplasmin, leading to ceruloplasmin deficiency