Presentation: Patient with copper overload
The most common causes of chronic liver disease in the United Kingdom are alcohol-related liver disease, metabolic dysfunction-associated steatotic liver disease and viral hepatitis. However, in a minority of cases there will be a genetic cause, including excessive copper deposition.
Example clinical scenario
A 33-year-old man presents with tremor and jaundice. His partner remarked about emotional lability recently and noticed a change in the character of his speech. He has a family history of liver disease. He consumes 12 units of alcohol per week on average. A non-invasive liver screen is negative apart from a low caeruloplasmin (<50% of lower limit of normal). 24-hour urinary copper excretion is high (>1.6μmol/24-hour). Cirrhosis is evident on ultrasound imaging. The ophthalmologists confirm that he has Kayser-Fleischer rings on slit lamp examination.
When to consider genomic testing
- If a patient presents with abnormal liver blood tests with or without additional neurological symptoms, consider genomic testing if you have a high suspicion of Wilson disease, as evidenced by:
- low levels of caeruloplasmin;
- high levels of liver copper;
- high levels of urinary copper;
- high levels of free copper; and/or
- Kayser-Fleischer rings.
What do you need to do?
- Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
- For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
- The appropriate panel to choose is:
- R172 Wilson’s disease: This is a single gene sequencing test that examines the ATP7B gene.
- None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion, or RoD) form.
- The majority of tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
- If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
- Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the test directory to confirm the right test for your patient.
Resources
For clinicians
References:
- European Association for the Study of the Liver. ‘EASL Clinical Practice Guidelines: Wilson’s disease‘. Journal of Hepatology 2025: volume 82, issue 4, pages 690-728. DOI: 10.1016/j.jhep.2024.11.007
- Newsome PN, Cramb R, Davison SM and others. ‘Guidelines on the management of abnormal liver blood tests‘. Gut 2018: volume 67, issue 1, pages 6–19. DOI: 10.1136/gutjnl-2017-314924.
- Shribman S, Marjot T, Sharif A and others. ‘Investigation and management of Wilson’s disease: a practical guide from the British Association for the Study of the Liver‘. Lancet Gastroenterology & Hepatology 2022: volume 7, issue 6, pages 560–575. DOI: 10.1016/S2468-1253(22)00004-8
For patients
- British Liver Trust: Wilson’s Disease
- Wilson’s Disease Support Group – UK