ISSN 2398-2969      

Copper toxicosis (Bedlington Terrier)

icanis
Contributor(s):

Kyle Braund

Penny Watson

Synonym(s): Copper storage disease


Introduction

  • Excessive storage of copper in liver.
  • Cause: autosomal recessive inheritance homozygous deletion in COMMD1 gene. Some affected Bedlingtons do not have the deletion and have more complex inheritance.
  • Signs: hepatitis (acute or chronic) progressing to cirrhosis if not treated, rarely hemolytic crisis.
  • Diagnosis: liver biopsy and copper stains/quantification.
  • Treatment: copper chelating agents, eg D-penicilliamine. Supportive: diet; anti-oxidants; zinc when chelation stopped.
  • Prognosis: reasonable, some → cirrhosis.
  • See also: Liver: acute disease and Liver: chronic disease - overview.

Pathogenesis

Etiology

  • Inherited tendency to accumulate copper in liver. Classical disease autosomal recessive due to large exon deletion in COMMD1 gene. Not recognized in any other breed. Recently affected Bedlingtons reported without this deletion: other genes likely involved and may be polygenic. 

Pathophysiology

  • An inherited metabolic defect in copper excretion from the liver. Other organs not affected (unlike human equivalent, Wilson’s disease). COMMD1 involved in protein degradation and deletion may reduce activity of key copper transporting protein ATP7B (cross reference Labrador hepatitis) reducing copper transport in to bile. 
  • Copper accumulation in hepatocytes results in oxidative damage → hepatocyte injury and death → acute and chronic hepatitis. Small/moderate amounts of copper → chronic liver injury → cirrhosis. Large amounts of copper → severe acute hepatic necrosis → copper release in to circulation → hemolytic crisis (uncommon). 

Timecourse

  • Variable.
  • Affected dogs can be asymptomatic or show signs of acute hepatic necrosis, chronic hepatitis or cirrhosis.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Kim Y G et al (2016) Prevalence and Clinical Relevance of Exon 2 Deletion of COMMD1 in Bedlington Terriers in Korea. J Vet Intern Med 30, 1846-1850 PubMed
  • Materia S et al (2012) Clusterin and COMMD1 Independently Regulate Degradation of the Mammalian Copper ATPases ATP7A and ATP7B. J Biol Chem 287(4), 2485-2499 PubMed
  • Forman O P et al (2005) Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Anim Genet 36(6), 497-501 PubMed
  • Coronado V A et al (2003) New haplotypes in the Bedlington terrier indicate complexity in copper toxicosis. Mammalian Genome 14(7), 483-491 PubMed
  • Sluis B van de et al (2002) Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet 11(2), 165-173 PubMed.

Other sources of information

  • Webster C R L et al (2019) ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs. J Vet Intern Med 33, 1173-1200 PubMed.

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