Genetic basis of Hypokalaemia Periodic Polymyopathy (also known as Burmese hypokalemia) - is an autosomal recessive genetic disorder primarily affecting Burmese cats and related breeds (including Asian, Australian Mist, Bombay, Burmilla, Cornish Rex, Devon Rex, Singapura, Sphynx, Tiffanie, and Tonkinese). The condition is caused by a nonsense mutation in the WNK4 gene, which encodes the lysine-deficient protein kinase 4. This mutation (c.2902C>T) results in a truncated, non-functional form of the protein. The WNK4 protein plays a critical role in potassium and sodium ion transport balance in the kidney's distal nephron. Both copies of the mutant gene must be inherited for clinical disease to occur; carriers have one normal and one mutant copy and are asymptomatic but can pass the mutation to offspring.
Pathophysiology - The WNK4 mutation impairs potassium retention by the kidneys, leading to excessive potassium loss in urine (potassium-wasting nephropathy) and resulting hypokalaemia (low blood potassium). Potassium is vital for proper muscle cell function, and its deficiency disrupts muscle excitability, causing episodes of muscle weakness and pain. Episodes can be triggered or worsened by exercise, stress, or cold weather. Muscle dysfunction mainly involves the skeletal muscles, particularly those supporting the head and neck, but can affect the limbs and respiratory muscles in severe cases.
Complications - Episodic muscle weakness frequently starting in young kittens (2-6 months, sometimes noticed around 1 year). Classic clinical signs include ventroflexion of the neck (drooping head), muscle tremors, weakness, and difficulty walking or holding the head erect. Severe cases may involve collapse and respiratory paralysis, which can be life-threatening. Episodes can be intermittent, with normal periods lasting days to weeks. Elevated serum creatine kinase (CPK) levels during episodes indicate muscle damage. Some cats may improve spontaneously by 1-2 years of age. Without management, severe hypokalaemia can cause ongoing muscle damage and complications from respiratory compromise.
Why This Matters to Breeders and Vets - Genetic Testing: Available tests identify affected homozygous cats and carriers to prevent breeding two carriers, which has a 25% chance to produce affected kittens. Breed Preservation: Testing is especially important for Burmese and related breeds with known carrier prevalence. Clinical Management: Veterinary awareness helps in diagnosing episodic muscle weakness linked to hypokalaemia and implementing potassium supplementation protocols. Preventing Fatal Outcomes: Early diagnosis and treatment prevent severe, potentially fatal episodes such as respiratory paralysis. Breeding Strategies: Informed breeding decisions can eradicate the mutation and reduce disease prevalence over time.
Summary - Hypokalaemia Periodic Polymyopathy in Burmese cats is a recessively inherited disorder caused by a mutation in the WNK4 gene, leading to defective kidney potassium regulation. The disease manifests as episodic muscle weakness, particularly ventroflexion of the neck, in young cats. Early genetic testing and potassium supplementation are vital for managing affected cats and preventing severe complications. Breeders and veterinarians play key roles in identifying carriers and affected animals to control and potentially eliminate this debilitating condition from Burmese and related breeds.