Erythrocyte pyruvate kinase (PK) deficiency is the first and most common inherited erythroenzymopathy described in anemic dogs, cats, and humans. The PK enzyme plays a crucial role in the erythrocyte energy metabolism, and its absence causes severe hemolytic anemia, often misdiagnosed as autoimmune hemolytic anemia. Breed-specific PK-LR mutation tests have been reported for Basenjis, West Highland white terriers (WHWT), and Beagles (as well as cats). We report here on new PK mutations in the Labrador retriever and the Pug breed and provide a survey of canine PK deficiency studied at the PennGen Laboratory.

A nonsense mutation in exon 6 at position 276 was identified in the coding PK sequence of 2 Labrador siblings; both had severe chronic and highly regenerative anemia and developed severe osteosclerosis and hepatic hemochromatosis (extremely high ferritin and hepatic iron). Sequencing of the gDNA of an anemic Pug showed a missense mutation (V283A) also in exon 6. Both mutations are not tolerated in the PK protein structure leading to PK deficiency in erythrocytes.

A biased group of samples were received by PennGen for screening from dog breeds with known PK mutations. Among the 246 WHWTs, 9% and 35% were homozygous deficient and carriers respectively, with a mutant allele frequency of 0.26. The average age at the time of diagnosis was 1.5 years ranging from 2 months to 5 years of age; some dogs were from Europe and South America. Of the 68 Beagles studied, 35% were affected and 3% were carriers with a mutant allele frequency of 0.37. The average age at the time of diagnosis was 2 years ranging from 7 months to 9 years. Surprisingly, very few samples from Basenjis were received for screening, and none showed the mutant allele. While PK-deficient Basenjis lived historically < 5 years, WHWT and Beagles can reach 9 years of age. Moreover, DNA from several anemic dogs from other breeds, including Chihuahua, Spitz, Bergamasco and Dachshund with biochemically a likely PK deficiency were also examined; however, no mutations have yet been identified.

In conclusion, PK deficiency appears to be a common cause for hemolytic anemia in several dog breeds, and mutation testing makes screening simple to detect affected and carriers. PK deficiency should also be considered in dogs of other breeds, which may require the more cumbersome enzyme testing.

Supported in part by NIH grant RR02512.