Basenji Pyruvate Kinase Deficiency

A cause of hemolytic anemia

BACKGROUND

Basenjis: A breed considered by some to be the most ancient; it evolved from Asian wolves and found its way over to Africa where it came to be known as a dog of the pharoahs. Europeans first came into contact with this breed in the late 1800's and prized it for its intelligence and speed. They quickly came to be bred as hunting dogs and are often now placed into the hound group. The breed was established in Europe in the 1930s and transported to America where it was added to the AKC registry in 1943. Since then, it has maintained a fairly consistent level of modest popularity amongst hunters and families alike

DISEASE HISTORY

In the mid-late 1960's a relatively large number of American Basenji owners began taking their dogs to the vets complaining of lethargy in their animals. Testing showed a widespread occurence of heretofor unseen cases of hemolytic anemia in these pets. An article published in the Journal of the American Veterinary Medicine Association in 1969 researched the cause of this anemia and through testing discovered a familial link between many of the affected dogs. In 1971 a study conducted at Cornell University, determined that these cases of congenital hemolytic anemia where caused by a erythrocyte pyruvate kinase deficiency.

DISEASE PATHOLOGY

Pyruvate kinase is an enzyme that catalyzes the final step in glycolysis, a process that converts glucouse, which acts as a poison in a living body, into pyruvate, a safer, more accessible form of energy. Basenjis who are deficient in this enzyme have a lower erythrocyte (RBC) life span, severe reticulosis (increase in immature RBCs), type 2 autohemolysis (breakdown of blood cells), and splenomegaly (enlarged spleen). These traits are all consistent with hemolytic anemia and mirror those found in humans who have a pyruvate kinase deficiency. In addition, basenjis deficient in PK also have an increased osmotic fragility to their RBCs and lower lactate:glucose ratios than healthy dogs.

Symptoms and Diagnosis

Basenjis with pyruvate kinase deficiency are often slow to develop and are often weak and show an aversion to exercise. Other easy to identify symptoms are the enlarged spleen and pale mucous membranes. A combination of these factors should lead a veterinarian to draw blood to do a hematological analysis which will confirm the diagnosis.

Mode of Inheritance and Genome

Pyruvate kinase deficiency is an autosomal recessive trait. While both parents are carriers of the trait and do display a slight decrease in enzyme activity, they are considered to be clinically unaffected. The rate of inheritance in offspring based on whether or not the parent is homozygous normal, a heterozygous carrier, or homozygous affected is shown below.

Problems and Solutions

Basenjis with a PK deficiency usually begin to show signs of the condition from 4 months to a year in age. Unfortunately, over time affected individuals begin to have developmental changes that result in their bone marrow being replaced with fibrous tissue, which results in a hardening of bone density. It is therefore not uncommon for these dogs to die by the age of four years due to bone marrow failure or liver disease.

The only potential treatment is a bone marrow transplant which is expensive, risky, and no guaranteed cure. The only real solution is to remove carrier dogs and afflicted dogs from the breeding population. There is an easy DNA test that can be done to determine if a dog is a carrier or affected by the condition and it can be conducted at any age level.

Opinion

It should be required that breeders of basenjis have their dogs genetically tested for a pyruvate kinase deficiency. Given that it is such an easily preventable condition and such a simple action could prevent its continued existence, there is no excuse not to do it. All owners of the breed should be informed by their veterinarians of the potential risk and have their blood tested at an early age. Any owners who choose not to spay or neuter their pet should also have a genetic test strongly recommended.

References

Berg, J.M., Tymoczko, J.L., Stryer, L. Biochemistry. New York: W.H. Freemand and Company. 2007.


Gultekin, et al. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs. J Vet Intern Med. 2012. 26(4):935-944.


Searcy, G.P. and Tasker, J.B. Congenital Hemolytic Anemia in the Basenji Dog Due to Erythrocyte Pyruvate Kinase Deficiency. Can J Comp Med. 1971. 35(1):67–70.


Tasker, et al. Familial anemia in the Basenji dog. J Am Vet Med Assoc. 1969. 154(2):158-65.


Whitney, K.M. and Lothrop, C.D. Jr. Genetic test for pyruvate kinase deficiency of Basenjis. J Am Vet Med Assoc. 1995. 207(7):918-921.


University of Prince Edward Island. What is pyruvate kinase (PK) deficiency? Accessed 5/2/13 from http://www.upei.ca/~cidd/Diseases/clinical%20pathology/PK%20deficiency%20.htm.