Pyruvate Kinase Deficiency: Background, Breeds at Risk, Symptoms, and Treatment

Pyruvate kinase is an enzyme involved in the metabolism of red blood cells. When mutations in the PKLR gene occur, it reduces the functionality of this enzyme and affects the ability of red blood cells to survive and function properly. Learn about pyruvate kinase deficiency in cats, symptoms and treatment, and the cat breeds that are known to be at a higher risk for this condition.

What is Pyruvate Kinase (PK) Deficiency?

Pyruvate kinase (PK) deficiency is an inherited metabolic disorder that is caused by mutations (i.e., changes in the nucleotide sequence of a cat's DNA) in the PKLR gene.

In cats with PK deficiency, the lack of the pyruvate kinase enzyme leads to a reduced ability of red blood cells to produce energy and otherwise function properly. This subsequently results in a secondary condition called hemolytic anemia, where red blood cells in a cat's body are destroyed at a rate faster than they can be produced. 

What Are The Symptoms of PK Deficiency in Cats?

Cats suffering from PK deficiency with associated hemolytic anemia don’t have enough oxygen circulating to and through the tissues and organs of their body. As a result, they can experience any of the following symptoms:

• Lethargy, weakness, and/or collapse
• Decreased appetite and/or weight loss
• Diarrhea
• Pale gums that are sometimes yellow (indicates jaundice, though this is rare)
• Pale mucous membranes
• Poor coat quality
• Breathing problems
• Increased heart rate (tachycardia)
• Enlarged spleen 

The age of onset varies and symptoms can range from mild to life threatening in severity. However, studies indicate that cats with PK deficiency typically develop mild, chronic anemia that occurs intermittently.

Cat Breeds at a Higher Risk for PK Deficiency

The first documented report of feline PK deficiency was in an Abyssinian cat (Ford et al., 1992). The longhaired version of the Abyssinian cat, the Somali, as well as mixed-breed domestic shorthair, are also known to be at a higher risk for the disease.

However, a 2012 study concluded that genetic testing for PK deficiency, which can affect both male and female cats, is also recommended for the following breeds:

• Bengals
• Egyptian Maus
• Maine Coons
• LaPerms
• Norwegian Forest Cats
• Siberian Cats
• Singapuras
• Savannah Cats

Genetics of PK Deficiency

A cat has 18 pairs of autosomal (non-sex) chromosomes and one pair of sex chromosomes. For each chromosome pair, one comes from the mother and one comes from the father. Chromosomes are named, and the PKLR gene associated with the potential for inherited PK deficiency is located on a cat's chromosome F1. You can see this chromosome toward the bottom left of the shaded side of Figure 1 below.

Figure 1. Graphical representations of each chromosome and trypsin Giemsa-banded staining of the chromosome pairs in domestic cats (Felis catus). Names of chromosome follow the convention of Wurster-Hill and Gray (image taken from O’Brien and Nash, 1982).

PK deficiency is an autosomal recessive disorder. Let's break down what this means:

• “Autosomal” refers to a gene that is located on one of the numbered non-sex chromosomes, in other words, on any but the X, Y chromosomes seen in Figure 1.
• “Recessive” means that two copies of the mutated gene are needed to cause the disorder.
• Cats have two copies of every gene—one from each parent. For a cat to be affected by PK deficiency, their mom and their dad would each have to pass down one copy of the mutated PKLR gene. 

However, cats that receive only one copy of the mutated gene (i.e., from only one parent, not from both) become carriers of the disease. Carrier cats are not affected by the disease and otherwise present as healthy.

Genetic testing for PK deficiency is important if there are plans to breed cats (especially with higher risk breeds). The University of Bristol provides graphical representations called Punnett squares that show all of the possible outcomes of breeding normal, carrier, and affected cats when it comes to PK deficiency. Normal cats with no mutations in the PKLR gene are represented by (-/-), carrier cats with one copy of the mutation by (+/-), and affected cats with two copies of the mutation (+/+). For example, if two carrier cats are bred, it results in 25% of offspring affected by PK deficiency (represented in the top red square in the 3rd "mating to avoid" Punnett square).

Figure 2. Graphical representations using Punnett squares to show all possible outcomes of a genetic cross for normal cats, cats that are carriers of PK deficiency, and cats that have PK deficiency (including matings to avoid) Provided by Langford Vets of the University of Bristol (2021). 

Diagnosis of PK Deficiency in Cats

The symptoms of PK deficiency in cats can be similar to those of other types of anemia, making diagnosis challenging. This means that a veterinarian will perform a range of tests to make an accurate diagnosis.

For a cat suspected of having PK deficiency, a veterinarian will thoroughly review a cat's medical history, conduct a thorough examination, and evaluate any symptoms. It is always best to communicate to your vet about when symptoms began, their severity, and how long they last (if not current).

Testing

A veterinarian will perform a range of tests that will typically include:

• Complete blood count (CBC). This test provides information about the different cell types in a cat's blood and can indicate the presence of disease. It specifically gives data on the number, size, and shape of red blood cells, white blood cells, and platelets.
• Urinalysis. While this test provides information about the health of the kidneys and the urinary system, it can also uncover potential issues with other organ systems that may be indicators of a metabolic disease like PK deficiency. 
• Serum biochemistry profile. A serum biochemistry panel or profile is designed to investigate a specific concern and can help diagnose metabolic disorders such as PK deficiency and other conditions. 

Genetic testing is also recommended to support a definitive diagnosis, especially for Abyssinian, Somali, and Domestic Shorthair cat breeds. 

Treatment of PK Deficiency in Cats

There is no cure for PK deficiency in cats, and treatment of the condition depends on the severity of an affected cat's symptoms, as well as their age.

Treatment options may include blood transfusions, medications to manage symptoms, and in some cases, a bone marrow transplant. It is important to note that not all cats with PKD will show symptoms, and cats who are only carriers of the mutated PKLR gene can still live normal lives. If you suspect that your cat may have PK deficiency, you should consult with a veterinarian for a proper diagnosis and treatment plan that best meets your cat's needs.

Conclusion

We hope that this review of PK deficiency in cats, its causes, symptoms, and treatment was informative and helpful. Regular wellness visits to your veterinarian supports your cat's overall health, and if you believe that your cat is suffering from a potential health issue it's always best to contact your vet right away. Genetic testing also provides the chance to detect certain diseases such as PK deficiency sooner, along with more opportunities for treatment and informed decision making. As discussed in this blog, this is especially important when it comes to decisions about breeding to prevent passing a genetic disease on to the next generation.

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