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Canine Pyruvate Kinase Deficiency (PK) - Pug Type
| Acronym: | PKD, PKDef, PK Deficiency |
| Gene: | PKLR |
| Mutation: | c.848T>C |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Canine Pyruvate Kinase Deficiency (PK Deficiency) is a genetic disorder characterized by low levels of pyruvate kinase enzyme in the red blood cells. The disorder was first documented in Basenjis, and it is the most common inherited erythroenzymopathy in dogs. PK deficiency has been reported in dogs, cats, and human beings. Several breeds are more prone to the disorder, such as Basenji, Beagle, West Highland White Terrier, Cairn Terrier, Miniature Poodle, Dachshund, Chihuahua, Pug, and American Eskimo dogs. Reed blood cells, known as erythrocytes, have an important role within the body to deliver oxygen to the body tissues via blood circulation through the cardiovascular system. An enzyme important for the proper function of erythrocytes is the pyruvate kinase (PK), which acts as a regulatory enzyme in anaerobic glycolysis and energy generation. PK catalyzes the last step of glycolysis, in which phosphoenolpyruvate is converted to pyruvate. A deficiency in pyruvate kinase results in red blood cells with decreased energy. In such red blood cells, ATP needed for energy cannot be synthesized, and cellular death occurs.
Symptoms of canine pyruvate kinase deficiency develop between 4 months to one year of age. Affected dogs suffer from severe hemolytic anemia. Typical PK deficiency symptoms are exercise intolerance, episodes of severe weakness, rapid heart rate, heart murmurs, pale gums, and stunted growth. The erythrocytic osmotic fragility curves appear in a normal sigmoid shape. When measuring iron levels affected dogs show severe hyperferritinemia (high levels of ferritin in the blood) and high serum iron concentrations. Radiography examination shows increased cortical bone and increased blotchy bone density in the marrow areas. Ultrasound of the abdominal area shows liver and spleen enlargement, a condition known as hepatosplenomegaly. Osteosclerisus of the long bones may be present as well. Necropsy findings include diffuse icterus, dense cortical and trabecular bone, and scant bone marrow which sinks in water. Bone marrow analysis reveals erythroid hyperplasia, mild fibroplasia, and hemosiderosis. Affected dogs usually die between 1 to 4 years of age because of progressive anemia and hepatic failure. PK deficiency clinical signs show progressive nature and affected dogs usually need to be euthanized. Canine Pyruvate Kinase Deficiency is associated with PK-LR gene mutation. The disorder is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Gultekin GI, Raj K, Foureman P, Lehman S, Manhart K, Abdulmalik O, Giger U. Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and seconday hemochromatosis in dogs. J Vet Intern Med. 2012 Jul-Aug;26(4):935-44.