What is Phosphofructokinase Deficiency (PFKD) in dogs?

Phosphofructokinase Deficiency as the name implies is a lack of the enzyme Phosphofructokinase in affected dogs. This results in a lack of ability to metabolise glucose into energy available for the cells to use when they need it quickly. This has a great effect on the affected dogs in times of heightened emotion such as great excitement and fear. Phosphofructokinase Deficiency also destroys red blood cells, leading to anaemia in affected dogs. It has an autosomal recessive pattern of inheritance.

Genetics of Phosphofructokinase Deficiency in dogs

Having an autosomal recessive pattern of inheritance means that affected dogs must have 2 mutated copies of the gene responsible for the dog to be considered genetically affected by Phosphofructokinase Deficiency. The gene responsible in this case is the PFKM gene that has the instructions necessary for the body to manufacture the enzyme Phosphofructokinase. Carrier dogs with only one copy of the mutated PFKM gene are able make enough of the enzyme to prevent being affected by the symptoms of Phosphofructokinase Deficiency.  So long as one parent dog is not a carrier of mutated PFKM genes, then none of the puppies in a litter will be affected by Phosphofructokinase Deficiency.

Severity of Phosphofructokinase Deficiency in dogs

Although in its untreated form, Phosphofructokinase Deficiency can be quite a severe disease, affected dogs that receive treatment at an early age will often lead lives of a normal length. The key is to identify the disease early and administer both veterinary treatment and environmental modification in combination.

What are the symptoms of Phosphofructokinase Deficiency in dogs?

Because the cells in dogs affected by Phosphofructokinase Deficiency lack the ability to turn glucose into usable energy fast and replace the energy used in a timely manner, cells that depend on this process are the first and hardest hit by the lack of Phosphofructokinase. The cells of the musculoskeletal system (muscles around the bones) show the greatest signs of stress. Affected dogs have a very low tolerance of exercise and may show evidence of muscle wasting and cramping. They may also be depressed with a fever and have generalised weakness over their body. Lethargy, hematuria (blood in the urine) and pale mucous membranes may result from the lack of functioning red blood cells. Affected dogs forced to exercise may suffer from muscle cell damage, jaundice and cramping.

How is Phosphofructokinase Deficiency diagnosed?

Phosphofructokinase Deficiency is often first suspected in dogs with very dark yellow to brown urine as the urine is contaminated with the products of the premature breakdown of blood cells and products. Affected dogs will also have clinical anaemia and very high levels of bilirubin in the urine. Obtaining a definitive diagnosis of Phosphofructokinase Deficiency from other similar Phosphofructokinase disorders requires a DNA Disease Screen for the mutated gene present in the affected dog.

Treatment of dogs with Phosphofructokinase Deficiency

Medical treatment of Phosphofructokinase Deficiency is somewhat limited but success has been found with bone marrow transplants, drug therapy and IV support after strenuous activity to limit muscle damage. Altering the affected dog’s living arrangements to avoid as much activity, stress and excitement as possible as proven to extend the length and quality of life to almost that of a healthy dog.

References

Gerber K, Harvey JW, D’Agorne S, Wood J, Giger U. Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. Vet Clin Pathol. 2009 Mar;38(1):46-51
Giger U, Reilly MP, Asakura T, Baldwin CJ, Harvey JW. (1986) Autosomal recessive inherited phosphofructokinase deficiency in English springer spaniel dogs. Animal Genetics. 17(1):15-23
Giger U, Smith BF, Woods CB, Patterson DF, Stedman H (1992) Inherited phosphofructo-kinase deficiency in an American cocker spaniel. Journal of the American Veterinary Medical Association 201: 1569-71
Harvey JW et al (1992) Characterization of phosphofructokinase-deficient canine erythrocytes. J Inherit Metab Dis 15:747–759
Inal Gultekin G et al (2012) Missense mutation in PFKM associated with muscle-type phosphofructokinase deficiency in the Wachtelhund dog. Mol Cell Probes 26(6):243-247
Skibild E, Dahlgaard K, Rajpurohit Y, Smith BF, Giger U. Haemolytic anaemia and exercise intolerance due to phosphofructokinase deficiency in related springer spaniels. J Sm Anim Pract. 2001;42:298-300
Smith BF et al. Molecular Basis of Canine Muscle Type Phosphofructokinase Deficiency. Journal of Biological Chemistry 271 (33): 20070-20074, 1996.