Copper metabolism disorders are genetic disorders of copper metabolism in the liver caused by mutations in two genes that code copper transporters – ATP7A and ATP7B. The ATP7A transporter is crucial for copper transport from fibroblasts into the liver and the ATP7B is crucial for copper export from the liver. Mutations in the ATP7A result in defective ATP7A transporter so the copper cannot be properly exported from fibroblasts and imported into the liver, causing a copper deficiency in the liver. That leads to Menkes disease which is a fatal neurodegenerative disease and is characterised by cerebral and cerebellar degeneration, failure to thrive, coarse hair and connective tissue abnormalities. Meanwhile the mutations in the gene ATP7B result in defective ATP7B transporter so the copper cannot be properly exported from the liver, causing a copper accumulation in the liver and secondarily in the brain. That leads to Wilson disease, which result in cirrhosis and neuronal degeneration in the middle-aged dogs. The mutation in ATP7A gene has X-linked inheritance and the mutation in ATP7B gene has an incomplete dominant inheritance. Disorders are present in Labrador Retrievers and Doberman Pinschers. However, in Doberman Pinschers mutations in both genes are found, but only the mutation in ATP7B can lead to a disorder, in that case Wilson disease. In Labrador Retrievers mutations can be present in only one or in both genes at the same time. Mutations in both genes at the same time can cause abnormally high copper accumulation which leads to copper toxicosis, especially in female dogs.

Inheritance: complex

Mutation: ATP7A and ATP7B gene

Genetic test: The method used for genetic testing is extremely accurate and allows complete differentiation between affected animals, carriers and healthy dogs. DNA testing can be done at any age.

DNA test sample: EDTA whole blood (1.0 ml) or buccal swabs. Detailed information about sampling can be found here.