Wilson disease, also known as hepatolenticular degeneration, is an autosomal recessive disorder that is caused by a deficiency of ATPase, an enzyme needed to transport copper from the liver to bile. As a result, copper accumulates first in the liver and then in brain, kidneys, bones, and corneas. Wilson disease affects approximately 1 in 30,000 people worldwide, with a carrier frequency of approximately 1 in 90 individuals.
Patients with Wilson disease may present with chronic liver disease, acute liver failure, hemolysis, and psychiatric or neurologic manifestations. Viral infection or drug toxicity may serve as a trigger for fulminant Wilson’s disease.
Neurologic symptoms include loss of fine motor coordination, ataxia, and dysphagia. Psychiatric manifestations occur in 20% of individuals. A characteristic ophthalmologic finding is the Kayser-Fleischer ring. Individuals with Wilson disease typically begin to show symptoms of liver dysfunction or neurologic disease in the first or second decade of life.
Acute liver failure in adults is characterized by a sudden loss of hepatic function without evidence of preexisting liver disease. Criteria for the diagnosis include the presence of coagulopathy (INR >1.5), hepatic encephalopathy, and an illness of less than 24 weeks’ duration.Pediatric patients with acute liver failure are less likely to present with encephalopathy. Modified criteria for the diagnosis of acute liver failure in children include evidence of acute liver injury and INR, >2.0 in the absence of encephalopathy.
Rapid diagnostic criteria for Wilson’s disease can be used in patients who present with acute liver failure. These criteria include a ratio of alkaline phosphatase (IU per liter) to total bilirubin (mg per deciliter) of less than 4.0 and a ratio of aspartate aminotransferase (IU per liter) to alanine aminotransferase (IU per liter) of greater than 2.2.
A variety of laboratory tests are recommended in the initial evaluation for Wilson disease. In approximately 95% of cases, serum ceruloplasmin is below normal. Additionally, patients with Wilson disease show decreased copper in serum and increased copper in urine.
The pathological diagnosis of Wilson’s disease is based on a liver biopsy that shows compatible histologic features and a positive copper stain. Unfortunately, the rhodanine stain does not always detect copper in the cytoplasm of hepatocytes. Copper quantification on either a dedicated core biopsy or a paraffin-embedded tissue block is considered to be the best available diagnostic test.
Mutation analysis may be helpful if routine tests are not diagnostic. A mutation in the ATP7B gene causes the deficiency in ATPase, that results in copper accumulation. More than 300 disease-causing mutations have been identified. Most mutations are family-specific with the exception of the H1069Q mutation, which accounts for >50% of identified disease alleles in the Northern European Caucasian population. Mutations are detected by PCR amplification of all 21 exons and a portion of the 5' untranslated region (UTR) DNA sequencing.
Gu YH et al. Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease. Clin Genet 2003;64(6):479-484.