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Wilson Disease

DNA/RNA
Test performed by: LabPLUS - Dept. Diagnostic Genetics - Molecular Genetics

Referral Requirements

Important Note:

Diagnostic: Specialist referral only.

Cascade: Genetic Services only.

Contact:

Genetic Health Service NZ can be contacted on 0800 476 123.

Specimen Collection
8 mL Adult EDTA Blood
4 mL Paediatric EDTA Blood
Note:

For paediatric samples a minimum of 0.5ml blood EDTA can be processed. (Microcollect)

Transport all bloods at room temperature within 24-48 hours. If necessary specimens can be refrigerated overnight for transport at room temperature the following day.

For testing of other sample types please contact the laboratory prior to sending.

Turnaround Time: 13 weeks
Contact Information
Contact Molecular Genetics via:

Lablink                                                    ext 22000

Mark Greenslade (Technical Head)   ext 22010

Pippa Grainger (Section leader)             ext 22014

Email: DGen@adhb.govt.nz

Background Information

Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to over 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.

Wilson disease is an autosomal recessive disorder caused by homozygous or compound heterozygous mutation in the ATP7B gene.

Diagnosis of Wilson disease depends upon the detection of low serum copper and ceruloplasmin concentrations, increased urinary copper excretion, the presence of Kayser-Fleisher rings in the cornea, and/or increased hepatic copper concentration.

ATP7B is the only gene known to be associated with Wilson disease. Testing may be targeted for some of the common mutations.

H1069Q is the only mutation found relatively frequently in populations of European origin. It accounts for 35-45% of Wilson disease alleles in a mixed European population and a greater percent in eastern Europe. The frequency of this mutation may be somewhat lower in probands with childhood onset and in probands presenting with liver disease.
R778L is the only relatively common mutation in Asian populations, accounting for approximately 57% of Wilson disease alleles in the Asian population younger than 18 years of age.
A single mutation, 15-bp deletion, has been identified in the 1-kb promoter, non-coding region and is common in Sardinia. Promoter mutations have not been described in other populations and are presumed to be rare.

For the New Zealand population full gene analysis is offered and targeted analysis is only performed on specific request. Complete gene sequencing detects mutations in about 98% of individuals with Wilson disease. If sequence analysis is negative deletion/duplication testing should be advised as although rare they have been reported. Large deletions and duplications, encompassing one or more exons, are rare, unlike the situation in the related ATP7A gene defective in Menkes disease. A deletion of exons 20 and 21 has been reported [Moller et al 2005].

Molecular genetic testing of ATP7B is available.

For more information about the Molecular Genetics service:

Molecular Genetics information page

Last updated at 15:49:04 22/03/2021