Pyruvate kinase deficiency (PKDef) is an inherited hemolytic anemia caused by a defect in the enzyme pyruvate kinase. Signs in affected dogs may include lack of energy and fatigue in dogs that appear otherwise fit.
Phenotype: Observable signs in affected dogs may include lack of energy, low exercise tolerance and fatigue in dogs that appear otherwise fit. Clinically, dogs with PKDef present with a severe anemia, increased iron levels, increased bone density, may have an enlarged spleen and liver as well as fibrous connective tissue replacement of bone marrow cells. Bone marrow and liver failure typically occur by 5 years of age.
Mode of Inheritance: Autosomal recessive
Alleles: N = Normal, K = Pyruvate kinase deficiency
Breeds appropriate for testing: Beagle, Cairn Terrier, Pug, West Highland White Terrier
Explanation of Results:
Dogs with N/N genotype will not have pyruvate kinase deficiency and cannot transmit this variant to their offspring.
Dogs with N/K genotype are not expected to show signs of pyruvate kinase deficiency but have half the normal level of pyruvate kinase activity, and are carriers. They may transmit this variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% pyruvate kinase deficiency-affected puppies.
Dogs with K/K genotype will have pyruvate kinase deficiency.
Dog DNA tests are carried out using cells brushed from your dog's cheeks and gums. The preferred cytology brushes are sent to you by mail, or you may provide your own brushes. For accepted alternative brushes, click here
We recommend waiting until puppies are at least three weeks old before testing.
Make sure the dog has not had anything to eat or drink for at least 1 hour prior to collecting sample.
When swabbing puppies, isolate each puppy from the mother, littermates and any shared toys for 1 hour prior to swabbing. Puppies should not have nursed or eaten for 1 hour prior to collecting sample.
If collecting samples from more than one dog, make sure to sample one dog at a time and wash your hands before swabbing another dog.
Label brush sleeve with name or ID of dog to be sampled.
Open brush sleeve by arrow and remove one brush by its handle.
Place bristle head between the dog’s gums and cheek and press lightly on the outside of the cheek while rubbing or rotating the brush back and forth for 15 seconds.
Wave the brush in the air for 20 seconds to air dry.
Insert brush back into sleeve.
Repeat steps 5 - 8 for each unused brush in sleeve on a fresh area of cheek and gums. Make sure to use and return all brushes sent by the VGL. In most cases, it will be 3 brushes per dog. If using interdental gum brushes, please note that the VGL requires 4 brushes per dog and only moderate or wide interdental gum brushes are accepted.
Do not seal brushes in sleeve.
Place all samples in an envelope and return to the address provided.
Do not collect saliva/drool – the key to obtaining a good sample is getting cheek cells on the swab
Do not rub swab on the dog’s tongue or teeth – this will result in poor quality sample
Do not collect a sample from a puppy that has recently nursed – the mother’s genetic material can rub off on the puppy’s mouth and contaminate the sample
Pyruvate kinase deficiency (PKDef) is an inherited hemolytic anemia caused by a defect in the enzyme pyruvate kinase. Loss of function of this enzyme results in premature death of red blood cells. Affected dogs do not have sufficient quantities of red blood cells to adequately supply the body with oxygen. Observable signs in affected dogs may include lack of energy, low exercise tolerance and fatigue in dogs that appear otherwise fit. Clinically, dogs with PKDef present with a severe anemia, increased iron levels, increased bone density, may have an enlarged spleen and liver as well as fibrous connective tissue replacement of bone marrow cells. Bone marrow and liver failure typically occur by 5 years of age. The disease is inherited as an autosomal recessive disorder thus both sexes are equally affected and two copies of the defective gene must be present for dogs to be affected. Carrier dogs, those with one defective and one normal copy, show no signs but have half the normal level of pyruvate kinase activity. Breeding two carriers is expected to produce 25% affected offspring and 50% carriers of the disease.
Different breed-specific mutations in the Pyruvate Kinase gene have been identified. Testing for the PKDef mutations found in Beagle, Pug, and West Highland White Terrier breeds can assist owners and breeders in identifying affected and carrier dogs. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs.
1 copy of the PKDef mutation. Dog is a carrier and unaffected but has half the normal Pyruvate Kinase activity of N/N dogs.
2 copies of the PKDef mutation. Dog is affected.
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.
Skelly, B.J., Wallace, M., Rajpurohit, Y., Wang, P., & Giger, U. (1999). Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency. American Journal of Veterinary Research, 60(9), 1169-1172. PMID: 10490091
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. doi: 10.1111/j.1939-1676.2012.00958.x