The inherited copper storage disease of Bedlington terriers (copper toxicosis, CT) was first recognized in a 1975 publication describing observations on 21 dogs. As of December 2002 there have been approximately 50 case reports and investigative studies on the copper storage disease in Bedlington terriers. The disease is due to a genetic abnormality that affects the ability of the liver to excrete the normal daily intake of excess dietary copper. Normal diets of all species of animals contain more copper than the body can utilize. In all animals there are normal genes that regulate the excretion of excess dietary copper. The liver plays a central role in utilization, storage and excretion of copper. The genes for copper excretion are responsible for production of a variety of proteins in the liver and it is the interactions of these proteins that regulates copper excretion from the liver. It is a single abnormal gene resulting in the production of an abnormal protein that is responsible for the failure of copper excretion from the liver and the resultant disease that some Bedlington terriers suffer.
The copper storage disease in Bedlington terriers is an autosomal recessive trait. This means that a dog must have two abnormal genes, one from the sire and one from the dam, before the liver will accumulate the excess copper. A heterozygous individual (one normal gene and one abnormal gene) will have a normal liver copper concentration. A heterozygous dog will never suffer liver damage from excess copper accumulation, but can pass the abnormal gene to his/her offspring.
The specific gene that is responsible for the disease in Bedlington terriers has not been identified. At this time the only unequivocal diagnosis of the disease is a liver biopsy with a quantitative copper analysis. Normal dogs of all breeds have a stable hepatic (liver) copper concentration throughout their lifetime. Even though the hepatic copper concentration is stable throughout the lifetime, normal dogs (of all breeds) vary considerably in their individual hepatic copper concentration. However, it is generally accepted that 400 parts per million on a dry weight basis (ppm dw) is the upper limit for the normal hepatic copper concentration.
There is some controversy about the optimal age for the time of the liver biopsy. The research to date indicates that the dog should be at least 12 months old before a reliable result can be obtained with a single liver biopsy. It has been documented that some heterozygous carrier dogs (one normal gene and one abnormal gene) will have an elevated hepatic copper concentration at 6 months of age, but the copper level will return to the normal range by 12 months of age. Therefore, if an elevated copper concentration is detected in a 6-month-old pup then an additional biopsy at one year of age would be required to prove whether the dog was a homozygous affected dog (two abnormal genes), or a heterozygous carrier dog (one normal gene and one abnormal gene). One additional problem with biopsy interpretation is that a rare carrier will have a copper concentration greater than 400 ppm dw its entire lifetime. One known carrier had a liver copper concentration of 1100 ppm dw her entire lifetime. However, homozygous affected dogs will commonly have 2000 ppm dw or greater by a year of age.
A DNA test is commercially available for the detection of the copper storage disease. The DNA test does not test for the specific gene that causes Bedlington terrier liver disease since that gene has not yet been discovered. Instead, the commercial DNA test actually tests for a disease marker. A "marker" is a short segment of DNA that has been discovered to be located on the chromosome close to the actual causative gene. The problem with markers is that they can move around on the chromosome and can have different locations in different lines of dogs. There are no published studies on the reliability of the DNA marker test. Anecdotal evidence suggests that there are some limits to the reliability. A DNA test will be unequivocal only when the actual gene for CT is discovered and a specific DNA test is developed that detects the specific CT gene. When the specific CT gene is discovered then the genetic DNA test will replace the liver biopsy as the preferred method of diagnosis.
All homozygous affected dogs (two abnormal genes) should be treated for their entire lifetime. There is some controversy regarding the appropriate treatment for affected dogs. Copper chelating agents and zinc are the two treatments that are proposed. No large follow-up studies in dogs are published on either treatment. Advice for owners is based largely upon studies in human patients with genetic copper storage disease (Wilson's Disease), and upon anecdotal evidence from dog breeders and veterinarians. The copper chelating agents are somewhat expensive and sometimes are difficult to obtain, but appear to be the more effective in extending the life of affected dogs. Copper chelating agents remove copper from the liver very slowly and affected dogs will require lifetime treatment. Affected dogs that are acutely ill from liver failure will not benefit from chelation therapy since the drugs work so slowly to remove excess copper.
The zinc treatment
is relatively new. Zinc has been shown to be effective in managing human
patients with copper storage disease once the hepatic copper concentration
has been lowered by chelation therapy. This same effect has not yet been
substantiated for dogs through scientific publications. Also, there is
evidence that zinc therapy will prevent the copper accumulation in affected
human patients if the therapy is started very early in life. Again, this
has not yet been substantiated for Bedlington terriers with CT.
In summary, copper toxicosis (CT) is an inherited disease in Bedlington terriers. The specific gene that causes the disease has not yet been discovered. As of December 2002 the most accurate diagnosis is made through the quantitative copper analysis of a liver biopsy from a dog that is at least 12 months old. At 12 months of age the homozygous affected dog (two abnormal genes) will commonly have a liver copper concentration greater than 2000 ppm dw while the homozygous normal dog and the heterozygous carrier dog will have hepatic copper concentrations less than 400 ppm dw. The majority of affected dogs will die from liver disease by 4 to 6 years of age if left untreated. The majority of heterozygous carrier dogs (one normal gene and one abnormal gene) will have a normal liver copper concentration at 12 months of age. However, a rare heterozygous carrier will have a mild elevation in the hepatic copper at 12 months (and throughout its lifetime), but heterozygous carriers never accumulate enough copper to suffer liver damage.