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.
PrintWilson 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.
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
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
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.
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
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: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
PRENATAL: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1840 | ATP7B Gene Sequence Analysis | 83891x1, 83894x26, 83898x26, 83904x33, 83909x33, 83912x1 |
| Technique | Days |
|---|---|
| ATP7B Gene Sequence Analysis | 10-21 |
1 Olivarez M et al. Ann Hum Genet. 2001;65:459-463.
2 Ala A et al. Lancet. 2007;369:397–408.
3 Wu ZY et al. Arch Neurol. 2001;58:971–976.
4 Gu YH et al. Clin Genet. 2003; 64:479–484.
5 Roberts EA, Schilsky ML. Hepatology.; 47(6):2089-2111.
6 Gu YH et al. Clin Genet. 2003;64:479-84.
7 Mak CM, Lam CW. Crit Rev Clin Lab Sci. 2008;45(3):263-290.
8 Kenney SM, Cox DW. Hum Mutat. 2007;28:1171-1177.
9 Merle U et al. Gut. 2007;56(1):115-20.