Diagnosis, management and genetic analysis of a cat with primary copper hepatopathy

CASE SUMMARY: A 2-year-old spayed female domestic longhair cat was presented for evaluation of chronic ocular discharge and occasional vomiting. While physical examination findings were consistent with an upper respiratory infection (URI), serum chemistry results revealed increased liver enzyme activities. Histopathologic examination of a liver biopsy identified substantial centrilobular accumulation of copper in hepatocytes – strongly suggestive of primary copper hepatopathy (PCH). Retrospective cytologic examination of a liver aspirate also identified copper aggregates in hepatocytes. After transitioning to a low-copper diet, 1 year of chelation therapy with D-penicillamine achieved normalization of liver enzyme activities and resolution of persistent ocular signs. Subsequently, a long-term regimen of zinc gluconate has been successfully managing the cat’s PCH for almost 3 years. Sanger sequencing of the cat’s ATP7B gene, which encodes a copper-transporting protein, revealed a novel, ‘likely pathogenic’, single nucleotide variation (c.3670t/a [p.Trp1224Arg]), for which the cat is heterozygous. RELEVANCE AND NOVEL INFORMATION: Recommendations are described for the long-term clinical management of feline PCH – a previously attainable but unreported outcome – with considerations for mitigating the speculated oxidation-exacerbated ocular risks of concurrent URI. This report is the first to include identification of copper aggregates in a liver aspirate from a cat – evidence that liver aspirates from cats could be routinely examined for copper as is standard practice for those from dogs. The cat is also the first reported with PCH and a ‘likely pathogenic’ heterozygous ATP7B genotype, which suggests that normal ATP7B alleles could be recessive to or incompletely/co- dominant with deleterious ATP7B alleles in cats, as has been reported in other species.