Copper storage disease / Copper toxicosis (CT) - Dobermann, Labrador Retriever*

Copper storage disease (copper toxicosis, CT) is a disorder of copper metabolism in which excessive amounts of copper accumulate in the liver. This can cause chronic liver inflammation (hepatitis) and, over time, lead to severe liver damage, liver cirrhosis or liver failure.

The disease usually develops gradually and often remains undetected for a long time. The first symptoms typically occur in middle-aged to older dogs. These include loss of appetite, weight loss, lethargy, weakness, vomiting and diarrhoea.

The risk of developing the disease is influenced by both genetic factors and diet. A variant in the ATP7B gene increases the risk of copper accumulation, while a variant in the ATP7A gene may have a partially protective effect in Labrador Retrievers.

What causes copper storage disease in dogs?

Copper is an essential trace element obtained through the diet. Excess copper is normally excreted by the liver through the bile.

In dogs with copper storage disease, this process is impaired. Excess copper gradually accumulates in liver cells, where it can cause inflammation and cellular damage.

Which genetic factors influence the risk?

Two genes play an important role in copper storage disease:

• ATP7B (risk factor): A variant in this gene impairs copper excretion and increases the risk of copper accumulation in the liver. Even one copy of the variant increases the risk, while two copies are associated with a considerably higher risk (autosomal additive inheritance).
• ATP7A (protective modifier): A variant in this gene can partially reduce copper accumulation in Labrador Retrievers, thereby lowering the risk of developing the disease. However, this protection is not complete. The effect depends, among other factors, on the dog's sex and the number of copies of the variant present (X-linked inheritance).

As the ATP7A gene is located on the X chromosome, the effect of the variant differs between male and female dogs:

• Male dogs (XY) have only one X chromosome and therefore only one copy of the ATP7A gene. If they carry the protective variant, it may have a stronger effect on copper accumulation in the liver than in heterozygous female dogs.
• Female dogs (XX) have two X chromosomes and therefore two copies of the ATP7A gene. If they carry the variant on only one X chromosome (heterozygous), the protective effect is usually less pronounced. This is because one of the two X chromosomes is inactivated in each cell, meaning that the protective variant is not active in all cells. However, if female dogs carry the variant on both X chromosomes (homozygous), the protective effect may be similar to that observed in male dogs carrying the variant.

Genetic risk assessment in Labrador Retrievers

Note: These simplified risk assessments apply to Labrador Retrievers and describe genetic tendencies rather than definite predictions of disease development. The protective effect is usually less pronounced in heterozygous females than in homozygous females or males carrying the ATP7A variant.

The ATP7A variant has also been identified in Dobermanns. However, a comparable protective effect has not yet been confirmed in this breed.

How is copper storage disease diagnosed and treated?

Early detection of copper accumulation is important, as liver damage may develop before obvious clinical signs appear. Veterinary blood tests, particularly the assessment of liver enzyme levels, can provide initial indications. A liver biopsy and measurement of the copper concentration in liver tissue may be necessary to reliably assess copper accumulation.

In affected dogs, a copper-restricted diet can help limit further copper intake. Zinc may also be used under certain circumstances, as it inhibits copper absorption in the intestine. Depending on the severity of the condition, medication to remove excess copper from the body may also be required.

Treatment should always be supervised by a veterinarian. Early diagnosis and appropriate treatment can slow disease progression and significantly improve the prognosis.

What is the significance of genetic testing for copper storage disease?

Genetic testing can identify the known variants in the ATP7B and ATP7A genes and help assess the genetic risk more accurately. The results can be used both for preventive healthcare and breeding decisions.

Important: An increased genetic risk does not necessarily mean that a dog will develop the disease. Conversely, dogs without the tested ATP7B variant may still develop copper storage disease, as other genetic factors and environmental influences also play a role.