Pyruvate kinase deficiency Flashcards
Explain the role of pyruvate kinase in the organism
Pyruvate kinase (PK) is one of the enzymes involved in glycolysis (breakdown of glycogen)
PK catalyses the conversion of phosphoenolpyruvate to pyruvate, producing one molecule of ATP in the process
What kind of cells are affected by PK deficiency and why
PK deficiency tends to affect cells like erythrocytes as they lack mitochondria
- thus ATP cannot be derived via the tricarboxylic acid cycle (= Krebs cycle)
What is the suspected pathomechanism for pyruvate kinase deficieny
In certain cats (Abyssinian, Somali and domestic shorthairs) the erythrocyte-specific isoenzyme of PK is deficient leading to energy depletion in the RBC
This results in a shorter survival time of the cell (hemolysis)
The reduced lifespan is thought to be due to dysfunction of ATP-deppendent processes such as Na+/K+ ATP-ase, leading to an accumulation of intracellular Na+
- the swollen RBCs become rigid and are removed by the spleen
What is the mode of inheritance of PK deficiency
PK deficiency is inherited in an autosmal recessive fashion, meaning that affected cats are homoozygous for the defective gene
What is the possible clinical course for affected cats
Affected cats may be:
- asymptomatic
- have chronic, mostly regenerative anemia or
- have intermittent hemolytic crises
Generally, clinical signs occur at less than 3 years of age, however older onset of signs has been documented
What are the typical clinical signs for PK deficiency
Typical clinical signs include:
- lethargy
- pale mucous membrane, pica
- icterus
- mild to moderate splenomegaly and occasional gastrointestinal signs
- some cats have significant anemia despite appearing outwardly healthy
What could trigger a hemolytic crisis
It is unclear what may trigger a hemolytic crisis
Stressful situations such as travel, infectious diseases, or giving birth have been iplicated
Why is it important to test all Abyssinian and Somali cats used for breeding
As both heterozygotes and homozygotes can be asymptomatic, it is recommended that all Abyssinian and Somali cats used for breeding be tested for the genetic fault
What is a frequent misdiagnosis in cats suffering PK deficiency
Hemolytic anemia caused by PK deficiency is often misinterpreted as immune-mediated hemolysis
Another disease that may mimic PK deficiency in Abyssinian in Somali cats is “increased osmotic fragility of RBCs”
What is an important recommendation for monitoring in cats suffering PK deficiency
Bilirubin cholelithiasis is more frequent in people with chronic hemolysis and this has been reported in a Somali cat with PK deficiency
Thus it is recommended that any PK-deficient cat be evaluated for extra-hepatic biliary duct obstruction if clinically jaundiced
What are the prognosis and therapeutic options in cats affected by PK deficiency
The prognosis is considered guarded
If the is experiencing frequent hemolytic crises or in cases of severe splenomegaly, splenectomy can be considered to remove the major site of RBC phagocytosis
It is also recommended that stressful situations be avoided
Blood transfusions may be necessary in severely anemic individuals
