Wilson Disease

Wilson disease is an inherited progressive disorder of copper metabolism, causing liver, neurological, and psychiatric symptoms. Accurate diagnosis is essential to ensure appropriate treatment in order to prevent and/or reduce the severity of symptoms. 


Wilson disease is an inherited progressive disorder of copper metabolism, causing liver, neurological, and psychiatric symptoms. Accurate diagnosis is essential to ensure appropriate treatment in order to prevent and/or reduce the severity of symptoms. 

Disease Name 
Wilson Disease
Disease Information 

Wilson disease is a progressive autosomal recessive disorder of copper metabolism, characterized by hepatic, neurological, and psychiatric symptoms. These usually appear between ages five to 35 years, but have been reported in people aged two to >70 years old.1 The disease occurs in 1/30,000 to 1/100,000 people worldwide; incidence varies among populations.2 It is estimated that about 1/100 people are carriers of the condition.

Clinical presentation of symptoms varies even between individuals within the same family. They are caused by the accumulation of copper in the bloodstream. Normally, the liver filters excess copper from the body and disposes of it in the bile in the digestive tract. Patients with Wilson disease cannot release the excess copper, which remains in the blood and accumulates in systemic organs, including the brain, kidneys, and eyes. Symptoms can appear as liver disease (recurrent jaundice, autoimmune-type hepatitis, hepatic failure, or chronic liver disease), abnormal neurologic findings (tremors, poor coordination, loss of fine-motor control, chorea or rigid dystonia), and psychiatric disturbance (depression, neurotic behaviors, disorganization of personality, and occasional intellectual deterioration). Kayser-Fleisher rings (copper accumulation in irides of the eyes) can also be seen.5 Early diagnosis and treatment with copper chelating agents or zinc will usually prevent or reverse the development of hepatic, neurologic, and psychiatric findings.6 Without treatment, Wilson disease is typically fatal.

Wilson disease is most commonly caused by mutations in the ATP7B gene. The most commonly seen mutation is H1069Q, accounting for 37-63% of mutations in Caucasians.3 The mutation R778L accounts for 57% of Wilson disease alleles in the East Asian population.4 There are more than 370 mutations reported worldwide, and most are rare and infrequent.8   

Testing Benefits & Indication 

Direct molecular testing remains the most decisive tool for making a diagnosis. This is because other testing (like biochemical analysis) may be unreliable, especially in children.9 Biochemical analysis is also not specific for Wilson disease because other liver diseases, such as cholestatic liver disease, can mimic Wilson disease.10 Biochemical testing may also be unreliable at detecting carriers of the disease.7

According to AASLD (American Association for the Study of Liver Diseases) practice guidelines, genetic testing for Wilson can be considered5:

  • On individuals in whom the diagnosis is difficult to establish by clinical and biochemical testing.5 An early diagnosis directly impacts medical management and allows implementation of treatment in a timely manner to optimize care for a patient.

Genetic testing for Wilson disease can also be considered:

  • For patients with liver abnormalities of uncertain cause, which are isolated or in conjunction with a neurological disorder.5
  • For testing other at-risk relatives, including children and prenatal testing for known familial mutations.
Test Description 

Our Wilson disease genetic testing includes Next-Generation sequencing (NGS) of the ATP7B gene. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using a standardized kit and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes, followed by polymerase chain reaction (PCR) and NGS. Additional Sanger sequencing is performed for any regions missing, or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.11 This test targets detection of DNA sequence mutations in all coding domains, and well into the 5’ and 3’ ends of all the introns and untranslated regions. 

Mutation Detection Rate 

Our Wilson disease test detects mutations in 90% of patients with clinical symptoms. Most (60%) are homozygous for ATP7B mutations, and 30% have only one abnormal allele. ~10% of patients have no detectable mutation.9 (clinical sensitivity). Ambry's ATP7B analysis can detect >99.9% of mutations in the gene, when present (analytical sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above on this page.

Prenatal: Prenatal testing is available. 


Turnaround Time 
1840 ATP7B Gene Sequence Analysis

14 - 28 


  1. Olivarez M, et al. Estimate of the frequency of Wilson's disease in the US Caucasian population: a mutation analysis approach. Ann Hum Genet. 2001;65:459-463.
  2. Ala A, et al. Wilson's disease. Lancet. 2007;369:397–408.
  3. Wu ZY, et al. Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in Chinese patients with Wilson disease. Arch Neurol. 2001;58:971–976.
  4. 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; 64:479–484.
  5. Roberts EA and Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008; 47(6):2089-2111.
  6. Patil M, et al. A review and current perspective on Wilson disease. J Clin Exp Hepatol. 2013; 3 : 321-36. 
  7. Kenney SM and Cox DW. Sequence variation database for the Wilson disease copper transporter, ATP7B. Hum Mutat. 2007;28:1171-1177.
  8. Merle U, et al. Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut. 2007;56(1):115-20.
  9. Sood V1, et al. Cholestatic liver disease masquerading as Wilson disease. Indian J Gastroenterol. 2015 Mar;34(2):174-7.
  10. Nicastro E, et al. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010 Dec;52:1948–1956.
  11. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.