Hypokalemic Periodic Paralysis

Hypokalemic periodic paralysis is a genetic disease that mainly affects young cats, causing periodic episodes of muscle weakness. The underlying cause is a mutation in the WNK4 gene, which plays a relevant role in the regulation of electrolytes in the body, especially potassium which is essential for proper muscle function.

Symptoms

Symptomatology of the disease usually manifests in the first year of life, approximately between 4 and 6 months of age. The most characteristic clinical sign is muscle weakness, which may occur periodically or sometimes constantly. During episodes, cats experience muscle pain on palpation, their gait becomes shorter and they may experience muscle tremors. Weakness is most pronounced in the cervical region, causing them to adopt a stooped posture with the head and neck tilted downward (ventroflexion), along with head bobbing.

Disease Management

Management of hypokalemic periodic paralysis focuses on potassium supplementation to correct hypokalemia and prevent episodes of muscle weakness. In addition, it is advisable to adjust the cat`s diet to avoid foods that may trigger symptoms.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected cat must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Hypokalemic periodic paralysis in cats, also known as Burmese hypokalemic polymopathy, is a genetic disease that mainly affects young cats, causing episodic or persistent muscle weakness. This condition is due to a mutation in the WNK4 gene, which plays a crucial role in regulating the balance of electrolytes such as sodium, potassium and chloride in the body. WNK4 is a serine-threonine kinase expressed mainly in the kidney, where it regulates sodium reabsorption and potassium excretion in the distal tubules. The causative variant is a nonsense mutation that generates a premature stop codon in the coding sequence, resulting in a truncated protein lacking an essential C-terminal region and the highly conserved Akt1/SGK phosphorylation site. This prevents WNK4 from functioning properly, leading to dysfunction in potassium homeostasis and the appearance of the characteristic clinical symptoms of the disease.

Most affected breeds

Burmese

Bibliography

Gandolfi B, Gruffydd-Jones TJ, Malik R, et al. First WNK4-hypokalemia animal model identified by genome-wide association in Burmese cats. PLoS One. 2012