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. References Chapman, B.L., & Giger, U. (1990). Inherited erythrocyte pyruvate kinase deficiency in the West Highland White Terrier. Journal of Small Animal Practice, 31, 610-616. Schaer, M., Harvey, J.W., Calderwood-Mays, M., & Giger, U. (1992). Pyruvate kinase deficiency causing hemolytic anemia with secondary hemochromatosis in a Cairn Terrier. Journal of the American Animal Hospital Association, 28(3), 233-239. Gultekin, G.I., Raj, K., Foureman, P., Lehman, S., Manhart, K., Abdulmalik, O., & Giger, U. (2012). Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs. Journal of Veterinary Internal Medicine, 26(4), 935-944.
Polycystic Kidney Disease in Cats
Bioguard Corporation Polycystic kidney disease (PKD) is a chromosomally dominant genetic disorder; it can occur in humans, cats, dogs, and other animals. In the renal cortex and medulla, there are cysts of various sizes and fluid-filled, so it is commonly known as the bubble kidney. Cysts increase in size and number over time, replacing kidney tissue and affecting their ability to filter waste from the blood, leading to chronic kidney failure. Pathogenesis Polycystic kidney disease is primarily caused by point mutations in the PKD1 gene, which is inherited as a dominant genetic disorder. The PKD1 gene plays a crucial role in regulating polycystin, a protein found on the cell membrane. A deficiency in PKD1 leads to underdevelopment of the renal tubules and collecting ducts in the renal cortex and medulla, preventing proper drainage of urine filtered by the renal glomeruli, which results in the formation of cysts characteristic of polycystic kidney disease. In the liver, this condition can also cause significant enlargement of bile ducts near the portal vein and may lead to bile duct fibrosis. Clinical symptoms Cats with polycystic kidney disease (PKD) are born with abnormal kidneys, though symptoms typically do not manifest until they are between 3 and 10 years old, with an average onset around 7 years. While the disease is present from birth, there are no noticeable symptoms in its early stages. Symptoms appear only when the disease progresses to a point where kidney tissue necrosis and kidney failure occur. As renal cysts enlarge over time, they compress the renal parenchyma, leading to irreversible kidney failure. Affected cats may experience a decreased appetite, weight loss, depression, and lack of energy. Clinical symptoms include increased thirst (polydipsia), frequent urination (polyuria), anorexia, vomiting, lethargy, and muscle twitching in the abdominal area. In severe cases, movement disorders (ataxia) or neurological issues may arise. Blood tests may reveal elevated blood urea nitrogen (BUN) and creatinine (CRE) levels, anemia, and high blood pressure. Early detection At present, it is possible to know whether cats have polycystic kidney disease through ultrasound testing and genetic testing. At 16 weeks of age, about 75% of cats with this problem had cyst-like structures on ultrasound scans, and by 36 weeks of age, 91% of cats had cysts. The accuracy of such a structure increases with age; generally speaking, when cats are over 10 weeks old, when using ultrasonic scanning, the accuracy can reach 90~95%. Genetic testing, which refers to the detection of its genotype, will be 100% accurate and can be performed at any age Breed predisposition Polycystic kidney disease mainly occurs in long-haired cats, and studies have shown that up to 38% of Persian cats have an abnormal PKD1 gene. Mainly affects cats of Persian and Persian-related breeds, such as Chinchillas, but other breeds such as Ragdolls, Scottish Folds, or other shorthair breeds such as Himalayans and Exotics have also been reported It is possible to have this genetic disorder. In addition, Meeks’s condition is relatively rare. References Schirrer L, Marín-García PJ, Llobat L. Feline Polycystic Kidney Disease: An Update. Vet Sci. 2021 Nov 8;8(11):269.
