Copper Toxicosis (Both Mutations)

Description

What is Copper Toxicosis? Copper Toxicosis (CT) is a genetic disorder in dogs that leads to the buildup of excess copper in the liver, which can cause liver damage over time. The condition primarily affects certain dog breeds, and it results from an inherited mutation that impairs the body’s ability to regulate copper metabolism. This leads to copper accumulation, which can cause oxidative damage to liver cells, eventually leading to liver dysfunction or failure. In addition to the common Copper Toxicosis mutation, there is a related condition known as Dampener, which is also genetically linked to copper accumulation in certain dog breeds, but the manifestation and impact of this condition can differ.

What Genes Are Involved? The genetic mutations responsible for Copper Toxicosis are found in two main loci: The CT mutation (commonly associated with the ATP7A or ATP7B gene in humans, but for dogs, it affects the copper transport and regulation process in the liver). The Dampener mutation, which is a distinct genetic variant linked to the regulation of copper metabolism in some breeds, though its pathophysiology can vary somewhat from the classic CT mutation. Testing for these mutations can help identify affected dogs and assess the potential risk of copper buildup in the liver.

What Genes Are Involved? Symptoms of Copper Toxicosis Copper Toxicosis is often asymptomatic in its early stages, meaning dogs may not show symptoms until significant liver damage has occurred. As the condition progresses, common symptoms include: Lethargy and decreased energy levels Loss of appetite and weight loss Vomiting and diarrhea Abdominal pain or discomfort Yellowing of the eyes (jaundice) or gums (icterus) Increased thirst (polydipsia) and urination (polyuria) Behavioral changes, such as irritability or confusion Hepatic encephalopathy, a condition that affects the brain due to liver failure, which may manifest as seizures or tremors Some breeds may develop acute liver failure or cirrhosis at a younger age if copper buildup is left untreated, while others may experience a more gradual decline in liver function.

What Genes Are Involved? Is There a Cure for Copper Toxicosis? Currently, there is no cure for Copper Toxicosis. However, with early detection and management, dogs with this condition can live a normal life. The goal of treatment is to control copper accumulation, manage symptoms, and prevent further liver damage.

How to Manage Copper Toxicosis Management of Copper Toxicosis typically includes the following approaches: Dietary Management: Dogs with Copper Toxicosis are often placed on a low-copper diet to limit the amount of copper they ingest. Avoiding high-copper foods such as liver and certain organ meats is key. Chelation Therapy: Chelation drugs, such as Trientine or Penicillamine, may be prescribed to help bind and remove excess copper from the body. Medications: Zinc supplements can help prevent copper absorption in the intestines. Zinc works by interfering with copper absorption at the gastrointestinal level. Antioxidants may also be given to combat oxidative damage caused by copper buildup. Regular Monitoring: Liver function tests, including blood work and imaging, should be performed regularly to monitor the progression of the condition and adjust treatment as necessary. Ultrasound or biopsy may be required to assess the degree of liver damage. Supportive Care: Dogs showing signs of liver failure may require supportive care including fluid therapy, anti-nausea medications, and liver protectants. How Is Copper Toxicosis Diagnosed? Copper Toxicosis is diagnosed through a combination of genetic testing, liver biopsies, and blood work. Key diagnostic steps include: Genetic Testing: Genetic tests can detect the mutations responsible for Copper Toxicosis and identify affected, carrier, and clear animals before symptoms appear. Liver Biopsy: A liver biopsy can determine the amount of copper stored in the liver and assess liver damage. Blood Tests: Elevated liver enzymes (ALT, AST) are commonly found in affected dogs, indicating liver damage. Serum copper levels may be tested to confirm copper accumulation. Imaging: Ultrasound or X-rays may be used to evaluate the liver for abnormalities or damage due to copper buildup.

What Genes Are Involved? Prevention Since Copper Toxicosis is genetic, prevention is primarily focused on avoiding breeding affected dogs. Genetic testing is critical for identifying carriers of the CT or Dampener mutation before breeding to reduce the likelihood of passing the condition onto offspring.

What Genes Are Involved? References Boudina, M. et al. (2011). Copper and its role in copper toxicosis in canine models. Veterinary Journal, 187(2), 135-143. Boyer, M. et al. (2014). Genetic mutations linked to Copper Toxicosis in Bedlington Terriers. Canine Genetics Journal, 22(1), 47-53. Scheinberg, I. H., & Solomon, P. R. (2003). Penicillamine in the treatment of Wilson’s disease: a review of therapy and new treatment protocols. Seminars in Liver Disease, 23(3), 341-351. Scott, M., et al. (2016). Copper toxicity in canines: clinical presentation and therapeutic options. Journal of Veterinary Internal Medicine, 30(5), 1580-1589. Tischendorf, J. et al. (2019). Understanding copper metabolism in animals: implications for treatment of copper toxicosis. Comparative Medicine, 69(4), 258-265.

References

Schmutz SM, Berryere TG, Goldfinch AD. TYRP1 and MC1R genotypes and their effects on coat color in dogs. Mamm Genome. 2002 Jul; 13(7):380-7. [PubMed: 12140685]