Pyruvate Kinase Deficiency in Basenjis by Maya Mazumder

HISTORY

mayammazumder9 — 2024-10-28 17:45:26 UTC

Starting in the 1960s, several veterinarians noticed a form of hemolytic anemia in Basenjis that seemed to be passed down through families. After noticing the similarities in their symptoms and clinical presentation to pyruvate kinase (PK) deficiency in humans, researchers began to focus on a possible mode of transmission and the expression of PK across individuals in these family lines.

GENETIC MUTATION AND TRANSMISSION

mayammazumder9 — 2024-10-28 18:11:34 UTC

The PKLR gene encodes for two different types of pyruvate kinase - the one found in the liver, as well as the one found in red blood cells. In Basenjis with PK deficiency, a single nucleotide deletion in the portion of this gene coding for the R-type enzyme leads to premature termination of the protein, rendering the R-type enzyme used in red blood cells nonfunctional.

PK deficiency is passed down in an autosomal recessive fashion. An animal must have two copies of the mutated PKLR allele to show clinical signs, as these animals cannot produce R-type PK at all. Animals with one copy of the mutated allele and one copy of a normal allele are nonclinical, but produce half of the PK of a non-carrier animal, and can pass down the mutated copy to offspring. Animals with two normal copies of the PKLR gene are not at risk of passing down PK deficiency to offspring and show normal levels of PK activity in red blood cells.

MECHANISM OF DISEASE

mayammazumder9 — 2024-10-28 18:20:44 UTC

PK deficiency causes chronic hemolytic anemia, meaning that there is a lack of red blood cells due to existing ones being broken down more quickly than normal. This is because the PK R-type enzyme is necessary for glycolysis within red blood cells, and without a functional version of this molecule red blood cells do not get enough ATP, shortening their life span. The high rate at which red blood cells die leads to a chronic lack of them circulating in the blood stream.

CLINICAL SIGNS AND PROGNOSIS

mayammazumder9 — 2024-10-28 18:34:37 UTC

As red blood cells deliver oxygen to the body, when there are not enough of these cells present, the body may not be getting the necessary oxygen to function. Animals will often present with extreme lethargy and exercise intolerance. They may also be jaundiced due to high levels of byproducts from the breakdown of abnormal RBCs. Upon clinical presentation, they may also have increased bone density (due to chronic changes in bone marrow), or show signs of iron overload in their tissues due to the constant breakdown of red blood cells. This disease typically manifests between 4 months and 2 years of age, and progresses over time, eventually leading to liver or bone marrow failure as the result of these systems being strained and damaged by red blood cell breakdown and the constant production of new cells over time.

PREVENTION OF PK DEFICIENCY

mayammazumder9 — 2024-10-28 18:42:34 UTC

Fortunately, there is now a genetic test for PK deficiency commercially available, which can screen animals to see if they are carriers or affected by the disease before breeding to prevent producing offspring with the disease.

DISCUSSION

mayammazumder9 — 2024-10-28 18:43:45 UTC

Despite the progressive, typically fatal nature of PK deficiency, the AKC and Basenji Club of America do not make a specific recommendation to test for this condition in Basenjis, nor mention it as a potential health problem for owners and breeders to be aware of. Are breeding clubs responsible for spreading awareness of this condition in Basenjis?

REFERENCES

mayammazumder9 — 2024-10-28 19:27:33 UTC

Andresen, E. 1977. Haemolytic anaemia in Basenji dogs. Hereditas. 85:211–214. doi:10.1111/j.1601-5223.1977.tb00968.x.
Basenji Dog Breed Information. Am. Kennel Club. Available from: https://www.akc.org/dog-breeds/basenji/
Health Statement. Available from: https://www.basenji.org/index.php/health-issues
Owen, J. L., and J. W. Harvey. 2012. Hemolytic anemia in dogs and cats due to erythrocyte enzyme deficiencies. Vet. Clin. North Am. Small Anim. Pract. 42:73–84. doi:10.1016/j.cvsm.2011.09.006.
Pyruvate kinase deficiency: MedlinePlus Genetics. Available from: https://medlineplus.gov/genetics/condition/pyruvate-kinase-deficiency/
Pyruvate Kinase Deficiency (PKDef) in the Basenji | Veterinary Genetics Laboratory. Available from: https://vgl.ucdavis.edu/test/pkdef-basenji
Whitney, K. Μ., and C. D. Lothrop. 1995. Genetic test for pyruvate kinase deficiency of Basenjis. J. Am. Vet. Med. Assoc. 207:918–921. doi:10.2460/javma.1995.207.07.0918.