Genetic basis of Pyruvate Kinase Deficiency in cats - is an inherited metabolic disorder caused by a mutation in the PKLR gene, which encodes the enzyme pyruvate kinase. This enzyme is crucial in the glycolytic pathway, playing an essential role in energy production within red blood cells. PKD is inherited as an autosomal recessive trait, meaning a cat must inherit two copies of the defective gene—one from each parent—to develop the disease. Cats with only one defective gene copy are carriers and typically asymptomatic but can pass the mutation on to offspring. The mutation often involves a particular single nucleotide polymorphism (SNP) located in an intron near exon 6, causing abnormal mRNA processing and a frameshift leading to a premature stop codon, which results in a nonfunctional enzyme. The frequency of this mutation is notably higher in certain breeds, especially Abyssinians and Somalis, but it has also been identified in many other cat breeds including Bengals, Egyptian Maus, Maine Coons, Norwegian Forest Cats, and others.
Pathophysiology - Pyruvate kinase is critical for producing ATP in red blood cells, which have no mitochondria and rely entirely on glycolysis for energy. When PK is deficient due to mutations, ATP production drops, impairing red blood cell function and leading to premature destruction (hemolysis). This causes a chronic hemolytic anemia where red blood cells are destroyed faster than they can be replaced. The severity and onset of clinical signs can vary greatly, ranging from subclinical to severe anemia.
Complications - Hemolytic anemia leading to lethargy, weakness, pale mucous membranes, jaundice, and poor body condition. Symptoms can appear anywhere from six months to five years of age, sometimes earlier. Anemia can be severe and life-threatening in some cats. Secondary effects include weight loss, poor appetite, diarrhea, and abdominal enlargement due to compensatory organ changes.
Why This Matters to Breeders and Vets - The disease is more common in Abyssinian and Somali cats but can affect various breeds. Genetic testing is essential for identifying carriers and affected cats to avoid breeding affected animals and reduce disease prevalence. Early diagnosis via genetic testing or clinical evaluation helps manage the disease and guide breeding decisions. Veterinarians need awareness to diagnose anemia early and support affected cats with proper treatment and monitoring. Breeders can use genetic screening to prevent producing affected kittens and improve the overall health of the breed population.
Summary - Pyruvate Kinase Deficiency in cats is an autosomal recessive inherited disorder caused by a mutation in the PKLR gene that leads to a deficiency of the pyruvate kinase enzyme in red blood cells. This enzyme deficiency disrupts energy production, causing premature red blood cell destruction and chronic hemolytic anemia. The disease is most frequently seen in Abyssinian and Somali cats but is also present in many other breeds. Clinical signs include lethargy, weakness, jaundice, and poor condition. Genetic testing is crucial for identification and breeding control.
