Pyruvate Kinase Deficiency

 

Gene: PKLR

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Beagle mutation: Substitution, PKLR gene; c.994 G>A, p.(G332S), exon7

Basenji mutation: Deletion, PKLR gene; c.433 del, p.(P145R fs STOP 23)

Labrador mutation: Substitution, PKLR gene; c.799 C>T, p.(Q267 STOP), exon6

Pug mutation: Substitution, PKLR gene; c.848 T>C, p.(V283A), exon6

West Highland White Terrier mutation: Insertion, PKLR gene; c.1333_1338 duplication, p.(K445_T446 duplication)

Medical system: Metabolic, blood

Breeds: Basenji, Beagle, German Shepherd, Labrador Retriever, Maltese Terrier, Pug, West Highland White Terrier

Age of onset of symptoms: Between 4 months and 2 years

Pyruvate kinase deficiency is a genetic metabolic disease seen in several breeds of dog, caused by different mutations found in the PKLR gene. The PKLR gene codes for the enzyme pyruvate kinase, which converts glycogen into energy, a metabolic reaction particularly necessary for red blood cell function.  In the case of a genetic pyruvate kinase deficiency, the lifespan of red blood cells is reduced, leading to hemolysis and anemia. Clinical signs in affected puppies include exercise intolerance, lethargy and slow growth. In addition, affected animals have pale gums (mucous membranes) and often have enlarged livers and spleens. In addition there is bone marrow loss, resulting in abnormal bone density.  More severe signs of liver and bone marrow failure appear around the age of 4, such as lethargy, loss of appetite, jaundice, neurological problems and immune complications.  Affected animals are usually euthanized at around 4 years of age due to poor quality of life, or die at around 5 years of age due to liver failure or chronic anemia.

 

References:

OMIA link: [0844-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Gulltekin GI, Raj K, Foureman P, Lehman S, et al. (2012) Erythrocytic pyuruvate kinase mutations causing haemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.  J Vet Intern Med 26:935-944. [pubmed/22805166]

Harvey JW. (2006) Pathogenesis, laboratory diagnosis, and clinical implications of erythrocyte enzyme deficiencies in dogs, cats, and horses. Vet Clin Pathol 35:144-56. [pubmed/16783707]

Skelly BJ, Wallace M, Rajpurohit YR, et al. (1999) Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency.  Am J Bet Res 60:1169-1172. [pubmed/22805166]

Whitney KM, Lothrop CD. (1995) Genetic test for pyruvate kinase deficiency of Basenjis. J Am Vet Med Assoc 207(7):918-921. [pubmed/7559024]

Whitney KM, Goodman SA, Bailey EM, Lothrop CD Jr. (1994) The molecular basis of canine pyruvate kinase deficiency. Exp Hematol. 22(9):866-74. [pubmed/7520391]

 

Contributed by: Anthony Daraiche and Nathan Groleau-Rouleau, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).