Pyruvate Kinase Deficiency in Dogs

Bioguard Corporation

Pyruvate kinase deficiency (PKD) is a hereditary genetic disorder that impairs the ability of red blood cells to metabolize properly. This defect leads to the destruction of red blood cells, resulting in severe hemolytic anemia. Affected animals can die from complications such as severe anemia and liver failure. The condition typically manifests between 4 months and 4 years of age, with common clinical signs including weakness, increased heart rate, and heart murmurs.

Pathogenesis
In mammals, mature red blood cells lack mitochondria, which means they cannot produce energy through oxidative phosphorylation. Instead, they rely on glycolysis to generate ATP, which is essential for maintaining cell shape and active transport across cell membranes. Pyruvate kinase (PK) plays a key role in the final step of glycolysis, where it catalyzes the conversion of phosphoenolpyruvate into pyruvate, producing ATP in the process (as shown in the diagram below).

When PK is deficient, red blood cells cannot synthesize sufficient ATP, leading to impaired cell metabolism. This energy deficit causes premature red blood cell death and results in hemolytic anemia. PKD is an autosomal recessive disorder caused by mutations in the PK-LR gene, which affects the activity of pyruvate kinase.

Clinical Symptoms
Pyruvate kinase deficiency (PKD) typically presents between 4 months and 4 years of age, causing severe chronic hemolytic anemia. Affected dogs may display symptoms such as exercise intolerance, severe limb weakness, easy fatigue, lethargy, underweight, pale gums, weight loss, emaciation, stunted growth, poor posture, and an increased heart rate. Ultrasound exams may reveal an enlarged liver and spleen, with common findings like bone sclerosis and hemosiderosis/hemochromatosis.

Treatment and Prevention
Currently, there is no effective drug treatment or way to slow the progression of PKD. The only treatment option is bone marrow transplantation, which may allow dogs to live a normal lifespan. However, this treatment is costly and carries a risk of death. Without treatment, affected dogs typically succumb to severe hemolytic anemia and liver failure. Genetic testing can identify PKD defects early in dogs and cats, enabling timely intervention and care.

Affected Breeds
Research indicates that certain dog breeds are more predisposed to inheriting PKD, including: Basenjis, Labrador Retrievers, Pugs, West Highland White Terriers, Cairn Terriers, Dachshunds, Terriers, Miniature Poodles, Chihuahuas, and American Huskies. Among cat breeds, Somali and Abyssinian cats are commonly affected, along with Egyptian Maus, LaPerms, American Shorthairs, Bengals, Maine Coons, Norwegian Forest Cats, Siberians, and Singapuras.

Genetic Detection
Genetic testing can determine whether dogs and cats carry PKD defects. Carriers may pass the gene on to offspring, so they should not be bred. If an animal tests positive for PKD, early monitoring and care are essential to manage the disease.