Copper Storage Disease

in Bedlington Terriers

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Description of Disease

Copper storage hepatopathy (liver disease) in Bedlington terriers is an inherited disease in which abnormally high amounts of copper accumulate within the tissues of the liver leading to cell damage and chronic inflammation (hepatitis). Ultimately this results in liver failure due to scarring (cirrhosis) of the liver and to death. Surveys during the 1980s and 90s indicated that 30 to 60% of Bedlington terriers were affected by this disease.


Three forms of the disease occur: Asymptomatic in which signs are yet to develop. Acute is seen in dogs up to six years of age, with the sudden onset of severe illness shown as depression, anorexia (not eating) vomiting and possibly jaundice (yellowing of mucous membranes, whites of eyes and skin). Chronic is seen in middle-aged dogs with signs of chronic liver damage and sometimes failure which may show vomiting, weight loss, jaundice and abdominal swelling.


The outlook for acutely ill dogs, even with treatment, is poor. There is a better prognosis for chronically ill animals if they are treated early enough. This disease does affect other breeds not just Bedlington terriers but they have the highest prevalence.

Photo of liver showing damage. It is hard to tell from the outside of a dog unless they have the acute form.
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Genetics of Disease

Copper storage hepatopathy in Bedlington terriers is an inherited autosomal recessive trait caused by a mutation in the COMMD1 gene, in which a large section of the gene has been deleted. Affected individuals have a pair of mutated genes (one from each parent). Carrier individuals have one mutated gene, and although unaffected themselves can pass on the disease to their offspring.


Until recently, although the identity of the mutated gene was known (and labelled COMMD1, a specific, reliable genetic test for the mutated gene did not exist. Instead a less reliable DNA satellite marker was used (called C04107) to identify dogs likely to have the mutated gene. This DNA marker had been shown to be linked to the occurrence of the disease, however, this test was not infallible and interpretation of the test was not straightforward.


Now, a test for the mutant COMMD1 gene has been developed. In the mutant gene a large area of DNA has been deleted from the COMMD1 gene (Forman et al 2005). The genetic test is available from the Animal Health Trust in the UK.

Genotypes

Being Autosomal recessive trait. The illustration shows how it could be passed but when two affected dogs breed they pass it on.


Mating a homozygous dominant dog with a heterozygous carrier dog yields:

  • –50% chance of homozygous dominant (CA free) offspring
  • –50% chance of heterozygous carrier offspring
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Mating two heterozygous carrier parents yields:

  • –25% chance of homozygous dominant offspring unaffected
  • –50% chance of heterozygous carrier offspring
  • –25% chance of homozygous recessive offspring affected

Treatments

  • Use of penicillamine to bind and increase excretion of copper
  • Zinc acetate helps to bind copper preventing absorption
  • Low copper diet with plenty of fluids
  • Vitamin E to help with liver damage.
  • Surgery could be used for some with more acute symptoms.

Prevention

To prevent this from spreading more screening should be done. All Bedlington terriers should have the COMMD1 gene test done to determine if they are affected or even a carrier. No breeding of those affected or carriers of the gene. This would help eliminate farther the disease in this breed. There is also a registry of those terriers who have had a liver biopsy after one year of age and been found to be unaffected. This is Canine Liver Registry at Purdue University.

Opinion

All dog breeders should have to start genetic testing their dogs. This disease could be held to very low number or close to eliminated if this was the case. Other diseases could also be controlled if this genetic testing was done. It would be pricy for many breeders but if they care for these animals then they would do what is best for them. Do you think this is something that is feasible if not what could be done to help remove this disease from the dog population?

References

Ettinger, SJ; Feldman, EC. Textbook of Veterinary Internal Medicine. 5th Ed. W.B. Saunders Company. Philadelphia, PA; 2000.


Schall, W.D. Use of Zinc Acetate for the Treatment and Prevention of Canine Copper Hepatotoxicosis. Kirk's Current Veterinary Therapy XII Small Animal Practice. W.B. Saunders Company. Philadelphia, PA; 1995.



Brewer, GJ, Dick, RD and Schall, W. Use of Zinc Acetate to Treat Copper Toxicosis in Dogs. Journal of the American Veterinary Medical Association. Volume: 201, Aug 15 1992.


Nantasanti, Sathidpak; Spee, Bart; Kruitwagen, and Hedwig S. Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids. Stem Cell Reports. Volume: 5, Nov 10 2015.


Hyun, Changbaig and Filippich Lucio John. Inherited canine copper toxicosis in Australian Bedlington Terriers. Journal of Veterinary Science Volume: 5, March 2004.


Animal Health Trust. “DNA Test for Copper Toxicosis in Bedlington Terriers.” http://www.aht.org.uk/cms-display/genetics_toxicosis.html Web 25 April 2016.


Forman OP, Boursnell ME, Dunmore BJ, Stendall N, van den Sluis B, Fretwell N, Jones C, Wijmenga C, Rothuizen J, van Oost BA, Holmes NG, Binns MM and Jones P Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Animal Genetics 36 April 2005.