Wilson Disease

Gene: ATP7B

Transmission: Autosomal recessive or dominant with incomplete penetration.

Mutations:

Mutation 1 : Substitution, ATP7B gene; c.3890 C>G, p.(T1297R), Chr.A1

Mutation 2 : Substitution, ATP7B gene; p.(P550L), Chr.A1

Mutation 3 : Substitution, ATP7B gene; c.3670 T>A, p.(W1224R), Chr.A1

Medical system: Liver, metabolic

Breeds: Domestic cat

Age of onset of symptoms: 9 months and older

In Wilson’s disease in the cat, a mutation in the ATP7B gene causes a deficiency in ceruloplasmin, a protein that transports copper into liver cells (hepatocytes). If this transporter protein is defective, copper begins to accumulate in the liver, leading to hepatocyte death. In the long term, excessive hepatic copper accumulation leads to primary copper-associated hepatopathy. Clinical signs include jaundice, lethargy, vomiting, weight loss, increased liver enzyme activity and chronic eye discharges. A rounded, irregular liver margin may also be seen on abdominal ultrasound and CT scans. A typical treatment plan aims first to stabilize liver disease by administering a penicillamine-based chelator, and then to prevent future copper accumulation by giving a low-copper diet combined with zinc gluconate.

To date, Wilson’s disease has been detected sporadically in the domestic cat population. The mutations associated with this disease are described as recessive or incompletely dominant, and there may be cases of heterozygous double states causing the disease. There is no evidence that the causative mutations are found in purebred cats.

References:

OMIA link : [1071-9685]

Recchia BK, Stokol T, Goto-Koshino Y, et al. (2023) Diagnosis, management and genetic analysis of a cat with primary copper hepatopathy. JFMS Open Rep 9:20551169231177275.  [pm/37427085]

Asada H, Chambers JK, Kojima M, et al. (2020) Variations in ATP7B in cats with primary copper-associated hepatopathy. J Feline Med Surg 22:753-759. [pm/31687873]

Asada H, Kojima M, Nagahara T, et al. (2019) Hepatic copper accumulation in a young cat with familial variations in the ATP7B gene. J Vet Intern Med 33:874-878.  [pm/30561139]

Contributed by: James Bérubé and Jérémy Groleau-Rouleau, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).