VHLGenetics has developed multiple genetic tests to diagnostically indicate the copper toxicosis disease. We test the copper toxicosis through multiple tests, including Copper Toxicosis (H701), Menkes disease (H824) and Wilson disease (H825). The tests are breed depended, in which the Copper Toxicosis test is available for the Bedlington Terrier. The Menkes disease test for the Labrador Retriever and the Wilson disease for both the Labrador Retriever and the Dobermann. The tests can be found on combibreed.com.
Copper Toxicosis (CT) is a hereditary disease and occurs due to toxic accumulation of copper (Cu) in the liver (Haywood et al., 2001). The accumulation of Cu leads to hepatitis and, ultimately, cirrhosis (Eriksson, 1983). The genes that are responsible for copper toxicosis are COMMD1, ATP7A and ATP7B, which are the genes that contain the mutations respectively for the genetic tests Copper Toxicosis, Menkes disease and Wilson disease (Forman et al., 2005) (Fieten et al., 2016). The COMMD1 gene is responsible for the regulation of copper homeostasis in the liver. The COMMD1 gene encodes for a protein family that is widely expressed and characterized by a specific domain called the COMM domain. The mutation in the COMMD1 gene causes a loss-of-function in the corresponding protein, and thereby subsequently leading to disruption in the copper homeostasis (Fedoseienko et al., 2014). Both P-type ATPases (ATP7A and ATP7B) are encoded by their corresponding genes ATP7A and ATP7B. The proteins preserve cellular copper homeostasis by expelling copper ions from the cell’s interior to prevent toxic accumulation. ATP7A is responsible for the secretory pathway, whereby copper is excreted in the bile and ATP7B is responsible for the copper-loading (Lenartowicz et al., 2016). From thereon, toxic accumulation can occur trough both ways either disruption in the secretory pathway or disruption in the copper-loading. The treatment of copper toxicosis involves mostly dietary changes and medications. The dietary changes are usually based on low copper diets. The most commonly used medicine is penicillamine. Penicillamine binds up copper and thereby causing the extra copper in the body to leave the body through the urine (Fieten et al., 2012).