Copper storage disease with intravascular haemolysis in a Bedlington terrier

Abstract

A 5-year-old male Bedlington terrier was found to have haemoglobinuria from intravascular haemolysis. The owners reported also recent vomiting, occasional diarrhoea, reduced activity and increased drinking and urination. A diagnosis of inherited copper storage disease, as previously described in this breed, was established by demonstrating characteristic light and electron microscopic changes and copper content of 7, 717 micrograms/g in biopsied liver. Treatment by chelation with d-penicillamine and a low copper diet was instituted and the dog remains well 10 months later. Intravascular haemolysis is rare in dogs and an uncommon finding in Bedlington terriers with copper storage disease.

Presumed primary and secondary hepatic copper accumulation in cats

“…This is consistent with the fact that hemolysis secondary to marked hepatocellular copper release and high plasma copper concentrations has only rarely been identified in Bedlington Terriers with copper-associated panlobular hepatic necrosis. 25 In this study, hepatocellular carcinoma and adenoma were detected in 2 cats with PCH (hepatic copper concentrations, 2,792 and 2,183 µg/g of dry weight), and hepatocellular adenoma was detected in another cat with secondary copper accumulation (hepatic copper concentration, 1,001 µg/g of dry weight); similar findings have not been previously reported, to the authors' knowledge. Interestingly, an association between high hepatic copper concentrations and hepatocellular carcinoma has been recently identified for humans with Wilson' s disease 4,26 and Long-Evans cinnamon rats that develop PCH.…”

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…The most common toxic injury causing CH in dogs is a consequence of hepatic copper (Cu) excess . Copper‐associated CH (CuCH) may develop in any breed, including mixed breeds, but the Bedlington Terrier (BT), Dalmatian, Labrador Retriever (LR), Doberman Pinscher, and West Highland White Terrier are predisposed.…”

“…In BT, autosomal recessive deletions in exon 2 of the ATP7B associated protein COMMD1 leads to CuCH . Copper concentrations can reach over 10 000 μg/g dry weight (dw) liver in this breed (normal hepatic Cu ranges from 120 to 400 μg/g dw) . Genetic screening for COMMD1 deletion, along with selective breeding in BT, has almost eliminated this disease.…”

“…Rarely individuals with high concentrations of hepatic Cu can undergo an acute necroinflammatory crisis releasing Cu and causing a Coombs' negative hemolytic anemia . Additionally, an acquired Fanconi‐like syndrome characterized by euglycemic glucosuria associated with renal Cu accumulation also can occur in some cases …”

“…[114][115][116] Copper concentrations can reach over 10 000 μg/g dry weight (dw) liver in this breed (normal hepatic Cu ranges from 120 to 400 μg/g dw). 18,19,24,26,35,37 Genetic screening for COMMD1 deletion, along with selective breeding in BT, has T A B L E 2 Factors implicated in the etiology of chronic hepatitis (CH) in dogs and the consensus panel's opinion on the relative strength of evidence (strong, moderate, or weak) based on both the scientific literature and clinical experience almost eliminated this disease. Recently, a candidate gene ABCA12…”