Test Detail

Liver disease due to progressive copper accumulation in hepatocytes. In the Labrador Retriever it behaves as a complex/multigenic disorder: a risk allele of ATP7B favours hepatic copper accumulation and modifier variants of ATP7A (X-linked) and RETN modulate the phenotype. Excess copper produces chronic hepatitis that may progress to cirrhosis and liver failure; the course is slow and early detection allows it to be managed with diet and chelators. In the New Zealand breeds Huntaway and New Zealand Heading Dog, the presence of the ATP7B risk allele has been documented in genomic screening, without a published clinical series of copper hepatitis in those breeds so far. The genetic test stratifies risk, but does not replace clinical follow-up or liver biopsy.

Copper hepatitis is a recognised cause of chronic hepatitis in the Labrador Retriever, with European lines especially affected. In Huntaway and New Zealand Heading Dog the presence of the ATP7B risk allele has been documented in genomic screening (PMID 40965331), but there are no published clinical series of disease in these breeds. Prevalence figures by breed are not consolidated (limited data).

- Test breeding animals for the available variants of ATP7B (risk) and ATP7A/RETN (modifiers), bearing in mind that ATP7A is X-linked
- Avoid mating two carriers of the ATP7B risk allele
- Do not abruptly remove all carriers if it compromises the genetic variability of the line: plan a gradual reduction
- Control the copper in the kennel diet (low-copper feeds, no unnecessary copper supplements)
- Monitor ALT annually in dogs of at-risk breeds/lineages and consider hepatic copper quantification in the event of persistent abnormalities

The diagnostic standard remains liver biopsy with copper quantification on a dry-weight basis; the genetic test stratifies risk but does not replace follow-up. In the Labrador the phenotype is complex: the presence of the ATP7B risk allele does not imply disease, and the ATP7A (X-linked) and RETN modifiers modulate accumulation. In Huntaway/Heading dog the available evidence is allele frequency in genomic screening, not confirmed clinical association. Differential diagnosis with other chronic hepatitis (infectious, toxic, immune), portosystemic shunt and storage hepatopathies. Treatment with penicillamine and zinc (the latter limits intestinal copper absorption) must be established by the specialist. Liver biochemistry in at-risk dogs allows early interventions that change the prognosis.

1. van De Sluis B, Rothuizen J, Pearson PL, et al. Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet 2002;11(2):165-73. PMID: 11809725
2. Fieten H, Gill Y, Martin AJ, et al. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Dis Model Mech 2016;9(1):25-38. PMID: 26747866
3. Wu X, den Boer E, Vos-Loohuis M, et al. Investigation of genetic modifiers of copper toxicosis in Labrador retrievers. Life (Basel) 2020;10(11):266. PMID: 33142854
4. Dirksen K, Fieten H. Canine copper-associated hepatitis. Vet Clin North Am Small Anim Pract 2017;47(3):631-44. PMID: 28063745
5. Smith F, et al. Survey of functional Mendelian variants in New Zealand Huntaway and Heading dog breeds. Anim Genet 2025;56(5):e70042. PMID: 40965331 | OMIA:001071-9615 (ATP7B), OMIA:002608-9615 (ATP7A) y OMIA:002609-9615 (RETN)