Copper‐Associated Liver Disease in Dalmatians: A Review of 10 Dogs (1998–2001)

Abstract

This retrospective study summarizes 10 Dalmatians suspected of having hepatic copper toxicosis. Hepatic copper toxicosis can result from either a primary metabolic defect in hepatic copper metabolism or from altered hepatic biliary excretion of copper. An inherited copper‐associated hepatopathy has been documented in Bedlington Terriers, and there is evidence for familial copper‐associated liver disease in West Highland White (WHW) Terriers and Skye Terriers. Nine of the 10 Dalmatians in this study presented for gastrointestinal clinical signs, including anorexia and vomiting. All animals had increased alanine aminotransferase (ALT) enzyme activity, and 9 of 10 had increased alkaline phosphatase (ALP) enzyme activity. The relative increase in ALT activity was much greater than the relative increase in ALP activity, suggesting a predominantly hepatocellular rather than cho‐lestatic liver disease. The mean hepatic copper concentration for 9 Dalmatians was 3,197 μg/g dry weight liver (dwl) (normal, <450 μg/g). In 5 of these 9 dogs, hepatic copper concentrations exceeded 2,000 μg/g dwl. Necroinflammatory alterations associated with copper‐laden parenchymal cells were the notable histopathologic finding. The inflammatory infiltrate was either primarily lymphocytic or neutrophilic. Morphologic features of cholestasis generally were not prominent except in those dogs with severe pathology. These findings lend support to the hypothesis that a primary metabolic defect in hepatic copper metabolism occurs in the Dalmatian breed. The mechanism and genetic basis of this condition require further study.