Episodic Hypokalemic Polymyopathy

 

Gene: WNK4

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, WNK4 gene; c.2899C>T, p.(Q967STOP), cat chromosome E1.

Medical systems: muscular, renal

Breed: Burmese

Age of onset of symptoms: usually between 2 to 6 months, sometimes as late as 2 years.

Episodic hypokalemic polymyopathy is a genetic disease seen in the Burmese breed, characterized by muscle weakness that presents episodically or incessantly.  The weakness can be severe and generalized to give muscle pain (myalgia) in a crouched posture.  More often the symptoms are associated with the cervical muscles to give head nodding, arched back and protrusion of the scapula.  Affected cats tend to have a short, low gait and are susceptible to tremors.

The genetic defect was identified in the WNK4 gene, which codes for an enzyme in the distal tubule cells of the kidneys involved in sodium and potassium recovery.  In the double mutated animal, there is an excessive loss of potassium in the urine, resulting in hypokalemia and the muscle symptoms seen in the clinic.  Treatment of an animal affected by an episode is with pharmacological supplementation of potassium.  This disease is seen in the Burmese breed, but the mutation has been detected in other breeds with genetics associated with Burmese.  DNA tests are available for the mutation in question to diagnose animals with symptoms, to identify carrier animals and to eliminate the mutation and the disease.

 

References:

OMIA link: [1759-9685]

Tamura S, Nakamoto Y, Tamura Y. (2023) Reversible positioning head tilt observed in 14 cats with hypokalaemic myopathy. J Feline Med Surg 25:1098612X231175761. [pubmed/37318332]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Brough A, Duchaussoy AC. (2021) A novel hypokalaemic polymyopathy and subsequent unrelated nutritional thiamine deficiency in a young Burmese cat. JFMS Open Rep 7:20551169211041930. [pubmed/34484804]

Malik R, Musca FJ, Gunew MN, et al. (2015) Periodic hypokalaemic polymyopathy in Burmese and closely related cats: A review including the latest genetic data. J Feline Med Surg 17:417-426.  [pubmed/25896241]

Gandolfi B, Gruffydd-Jones TJ, Malik R, et al. (2012) First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats. PLoS One 7(12):e53173. [pubmed/23285264]

 

Contributed by: Samantha Patterson and Sara Puligandla, Class of 2027, Faculté de médecine vétérinaire, Université de Montréal.   (Translation DWS).