Congenital copper storage disease in the dog
The innate copper storage diseases of the dog ( Kupfertoxikosen ) are hereditary diseases of the dog , which are characterized by an impaired excretion of copper. The most common mutation of the copper transport protein ATP7B , which corresponds to Wilson's disease in humans. But other genetic defects can also lead to an accumulation of copper in the liver. The Bedlington Terrier is most commonly affected, but such diseases also occur in other breeds.
Pathophysiology
Copper is one of the essential trace elements . It is transferred into the blood in the small intestine via copper transport proteins ( copper transporter 1 , CTR-1) and reaches the liver via the portal vein . Here it is bound to glutathione or metallothionein . If copper is required in the organism, it is released into the bloodstream via the transport protein ATP7B . Excess copper is also excreted into the bile via ATP7B, with the copper metabolism domain containing protein 1 (COMMD1) playing a role as a cofactor.
The most common genetic defect concerns the gene for ATP7B ("Wilson gene"), but other metal transporters such as ABCA12 can also be defective and lead to similar clinical pictures. They lead to an accumulation of copper in the center of the liver lobules and thus to oxidative damage to the mitochondria . This results in chronically active hepatitis , which eventually turns into cirrhosis of the liver . Occasionally, acute liver necrosis also occurs with the release of copper into the bloodstream and hemolysis as a result .
clinic
Signal element
Symptoms can in principle occur at any age; but mostly middle-aged dogs of the breeds Bedlington Terrier , Skye Terrier , West Highland White Terrier and Doberman are presented , whereby the disease occurs proportionally most frequently in the Bedlington Terrier. Cases have also been described in other breeds, including the Dalmatian , Keeshond, and Labrador Retriever .
Symptoms
The symptoms vary depending on the course of the disease. In the chronic form, slowly progressive loss of performance and emaciation are in the foreground, and jaundice may be present. A reduced liver is typical; and hepatic encephalopathy may occur. In acute liver necrosis with hemolysis , vomiting , anorexia and depression occur.
diagnosis
In addition to the usual signs of an acute or chronic liver problem , the diagnosis is made by a liver biopsy , in which a greatly increased copper concentration in the tissue can be determined. The normal value is below 400 µg / g, liver damage occurs at values above 2000 ppm. According to recent studies, the copper-zinc quotient in the urine can also be a useful criterion.
A DNA marker test is available for COMMD1-associated copper toxicosis in the Bedlington Terrier , which is also suitable for diagnosis.
Therapy and prognosis
Therapy is symptomatic and consists of a suitable reduced copper diet in conjunction with chelation of the copper with D-penicillamine or trientine , which enables excretion via the kidneys . The addition of zinc to the feed stimulates the formation of metallothionein in the intestine, which binds copper and prevents it from being absorbed into the portal blood. In addition, hepatitis and cirrhosis are also treated depending on the severity.
The prognosis for acute liver necrosis and hemolysis and in dogs with cirrhosis is poor. Dogs with mild to moderate liver failure have a moderately good prognosis. In the Bedlington Terrier, the copper content in the liver can be reduced within six months, in other breeds also faster. If diagnosed before hepatitis appears, the prognosis is good. Therapy is monitored by liver biospsia.
Genetics and Breeding Hygiene
The disease is described as simply autosomal recessive in the Bedlington Terrier , whereby, as mentioned, a DNA test is available, which can also be used to identify clinically healthy carriers. It is unclear to what extent this test is applicable to other breeds as well. If a non-Bedlington dog is diagnosed with copper toxicosis, it is recommended that its relatives undergo a liver biopsy so that preventive measures can be initiated. Without a DNA test, it is recommended that parents, first generation offspring and full siblings of a copper toxicosis dog be excluded from breeding.
literature
- DS Rolfe, ST Twedt: Copper-associated hepatopathies in dogs. In: Vet Clin N Amer Sm Anim Pr. 25 (2), (1995), pp. 399-417. PMID 7785171
- Vera M. Eulenberg et al .: The chronic hepatitis of the dog. In: Kleintierpraxis Volume 63, 2018, pp. 21–38.
