Wilson's Disease

Wilson's Disease (Wilson Disease) is a rare autosomal recessive disorder that results in copper build up in the brain and liver. There are both neuropsychiatric and GI/hepatic signs and symptoms.

• Wilson's disease occurs in about 1 in 30,000 people.
• Males and females are equally affected.
• The prevalence is higher in Japan.^[1]

• Symptoms usually begin between the ages of 5 and 35 years (average age of 17).

• If detected early and treated appropriately, individuals can have normal health and a normal lifespan.
• In untreated cases, the disease is progressive and disease can occur within 5 to 10 years (from severe brain damage, liver failure).
  • Severe hemolytic anemia can also be an unusual complication of Wilson’s disease.^[2]

• The clinical spectrum of liver disease can range from being asymptomatic to acute liver failure or cirrhosis
• Hepatic/GI symptoms include vomiting, weakness, ascites, edema, jaundice, and jaundice-associated pruritis.
• Adults may have additional neuropsychiatric symptoms which can include:
  • Neurologic symptoms such astremors, muscle stiffness, and aphasia
  • Psychiatric symptoms (present in about 15% of cases) such as personality changes, anxiety, hallucinations, psychosis, or depressive symptoms.

• Wilson's disease is an autosomal recessive disorder of copper metabolism in chromosome 13, due to a mutation in the Wilson disease protein (ATP7B) gene.
• Copper excretion by the liver is impaired in Wilson's disease
  • The defective biliary excretion of copper causes copper accumulation in tissues, particularly in the brain (basal ganglia), liver, and cornea^[3]

• In young patients presenting with tremors, one should always order:^[4]
  • Serum ceruloplasmin level (low, due to the shorter half-life of non–copper-bound ceruloplasmin)
  • Total serum copper (low, since serum ceroplasmin is low)
  • Free serum copper (elevated)
  • 24-hour urinary copper excretion (universally elevated in untreated individuals)
  • Ferritin levels (elevated)
• Liver biopsy will indicate elevated copper levels due to copper deposition
• Genetic testing for ATP7B gene variations can provide diagnostic confirmation if biochemical testing is not definitive

• CT head will often show signs of atrophic changes in the basal ganglia, cortical, and cerebellar regions that mimics neurodegenerative disease.
• MRI head will show increased signal in the basal ganglia and especially in the putamen

• Dysarthric speech is the most common neurological sign^[5]
• Patients will often appear jaundiced
• On gait exam, there is typically an ataxic gait
• A “wing-beating” tremor is commonly present as well
• Kayser-Fleischer rings, which represent copper deposits in the Descemet membrane of the cornea, are seen on ophthalmoscopic examination by slit lamp.
  • Kayser-Fleischer rings are a pathognomonic finding of Wilson disease but can be absent in around 50% of patients with Wilson disease.^[6]
  • Patients should be referred to an ophthalmologist for assessment.

• Treatment for stable symptomatic Wilson disease includes copper-chelating agents such as D-penicillamine or trientine.
  • Asymptomatic patients may be treated with lower doses of copper-chelating agents or with zinc salts that lower intestinal copper absorption.
  • Lifelong maintenance therapy and clinical monitoring is required when patients are on chelating agents or zinc.
• Patients with existing cirrhosis with synthetic dysfunction do not benefit from copper chelators