Molecular test for pyruvate kinase deficiency (PK Def), an autosomal recessive hereditary erythroenzymopathy caused by PK deficiency in the erythrocyte. Red blood cell half-life is shortened and it produces chronic regenerative hemolytic anemia, intermittent weakness, hepatosplenomegaly in the first year and, in advanced stages, osteosclerosis, myelofibrosis and bone marrow and liver failure. The test reports clear/carrier/affected status for the variant corresponding to each breed.

OMIA:000844-9615 lists variants in Basenji, Beagle, Cairn terrier, Chihuahua, Dachshund, Labrador retriever, Miniature Schnauzer, Miniature Poodle, pug, Toy American Eskimo and West Highland white terrier. In a biased sampling of anemic animals the mutant allele frequency was 0.26 in West Highland white terrier and 0.37 in Beagle (Gultekin 2012); these are not population estimates and must not be extrapolated.

- Chronic regenerative hemolytic anemia (macrocytic, hypochromic)
- Intermittent weakness and poor performance
- Hepatosplenomegaly before one year of age
- Progressive osteosclerosis and myelofibrosis
- Bone marrow and liver failure by around 5 years of age
- Jaundice and iron overload (secondary hemochromatosis)

PK Def was first documented in the Basenji, where Whitney et al. (1994) identified the causative mutation in PKLR (deletion of one nucleotide in exon 5). In 1999 Skelly et al. described the 6-bp insertion specific to the West Highland white terrier (shared by the Cairn terrier). In 2012 Gultekin et al. characterized additional specific variants (Labrador retriever, pug and Beagle) and confirmed that different breeds have different mutations. In 2025 Ma et al. described a splicing variant with exon 8 skipping in a Miniature Schnauzer. There is no single canine mutation: the test must select the variant of the animal's breed.

- Genotype breeding animals before mating, with the variant corresponding to their breed.
- Do not mate carrier x carrier (25 % risk of affected homozygotes); carrier x clear produces no affected animals and gives 50 % carriers.
- An affected animal must not be bred; a carrier can be mated to a clear animal without producing affected animals.
- After a confirmed clinical case, do not repeat the parental mating and communicate the status to the buyer.

Confirm with a complete blood count (regenerative, macrocytic and hypochromic anemia) and erythrocyte PK assay; the molecular test defines the genetic status, but the phenotype may be modulated by transfusion, iron deficiency or other anemias. Differential diagnosis with other hereditary hemolytic anemias (phosphofructokinase deficiency, pyrimidine 5'-nucleotidase deficiency) and with immune-mediated anemias. Symptomatic management: transfusion in crises, iron chelators and individual assessment of splenectomy.

1. Whitney KM, Goodman SA, Bailey EM, Lothrop CD Jr. The molecular basis of canine pyruvate kinase deficiency. Exp Hematol. 1994;22(9):866-874. PMID: 7520391.
2. Skelly BJ, Wallace M, Rajpurohit YR, et al. Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency. Am J Vet Res. 1999;60(9):1169-1172. PMID: 10490091.
3. Gultekin GI, Raj K, Foureman P, et al. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs. J Vet Intern Med. 2012;26(4):935-944. PMID: 22805166.
4. Ma TY, Kuo CJ, Liu PC. From Mutation to Manifestation: Evaluation of a PKLR Gene Truncation Caused by Exon Skipping in a Schnauzer Terrier. Animals (Basel). 2025;15(24):3634. PMID: 41463922.
5. OMIA:000844-9615. Pyruvate kinase deficiency of erythrocyte in Canis lupus familiaris. https://omia.org/OMIA000844/9615/