Wilson Disease

Wilson Disease is a progressive autosomal recessive disorder of copper metabolism, characterized by hepatic, neurological and psychiatric problems. It is estimated that 1/100 people are carriers.

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Wilson Disease is a progressive autosomal recessive disorder of copper metabolism, characterized by hepatic, neurological and psychiatric problems. It is estimated that 1/100 people are carriers.

The most commonly seen mutation is H1069Q, accounting for 37-63% of mutations in Caucasians. The mutation R778L accounts for 57% of Wilson Disease alleles in the East Asian population. There are more than 370 mutations reported world-wide, and most are rare and infrequent.

Our Wilson Disease testing should be considered in patients with liver abnormalities of uncertain cause which are isolated or occur with a neurological disorder. Direct molecular diagnosis remains the most decisive tool as biochemical analysis may be unreliable especially for carriers of the disease.

The Ambry Test: Wilson Disease is Gene Sequence Analysis that detects mutations in 90% of patients. Most (60%) have two ATP7B mutations, and 30% have only one abnormal allele. 10% percent of patients have no detectable ATP7B mutation.

Disease Name 
Wilson Disease
Disease Information 

Wilson disease is a progressive autosomal recessive disorder of copper metabolism, characterized by hepatic, neurological and psychiatric problems. Symptoms usually appear between ages five to 35, but new cases have been reported in people aged two to 72 years.1 It is estimated that 1/100 people are carriers. The disease occurs in 1/30,000 to 1/100,000 people worldwide; risks vary in different populations.2 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

Symptoms 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 the organs, including the brain, kidneys, and eyes. Symptoms can appear as liver disease (recurrent jaundice, autoimmune-type hepatitis, hepatic failure, or chronic liver disease), neurologic disorders (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 eyes) can also be seen.5 Early diagnosis and treatment with copper chelating agents or zinc, will prevent or reverse the development of hepatic, neurologic, and psychiatric findings.6

Testing Benefits & Indication 

Wilson disease testing should be considered in patients with liver abnormalities of uncertain cause which are isolated or in conjunction with a neurological disorder.5 Direct molecular diagnosis remains the most decisive tool as other testing, such as biochemical analysis, may be unreliable especially for carriers of the disease.7 There are more than 370 mutations reported world-wide, and most are rare and infrequent.8

Test Description 

This Ambry Test is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-21 of the ATP7B gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and in the 5’UTR at c.-422 and c.-129. Specific mutation analysis for individual ATP7B mutations known to be in the family is also available.

Mutation Detection Rate 

The Ambry Test: Wilson Disease detects mutations in 90% of patients. Most (60%) are homozygous for ATP7B mutations, and 30% have only one abnormal allele. Ten percent of patients have no detectable mutation.9

Specimen Requirements 

Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Minimum DNA Amount of 5μg of DNA at a concentration of ~100ng/μl in 50μl TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 20μg. Store frozen and ship on ice or dry ice. 
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.

Billing Codes 
Test Code Technique
1840 ATP7B Gene Sequence Analysis

 

Turnaround Time 
Technique Days
ATP7B Gene Sequence Analysis 20-42

 

Specialty 
Genes 
References 

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. [PMID: 11806854]

2. Ala A et al. Wilson's disease. Lancet. 2007;369:397–408. [PMID: 17276780]

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. [PMID: 11405812]

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. [PMID: 14986826]

5. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2009; 47(6):2089-2111. [PMID: 18506894]

6. Mak CM, Lam CW. Diagnosis of Wilson's disease: a comprehensive review. Crit Rev Clin Lab Sci. 2008;45(3):263-290. [PMID: 18568852]

7. Kenney SM, Cox DW. Sequence variation database for the Wilson disease copper transporter, ATP7B. Hum Mutat. 2007;28:1171-1177. [PMID: 17680703]

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. [PMID: 16709660]