Glycogen Storage Disease VII, Phosphofructokinase (PFK) Deficiency

 

Gene: PFKM

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Cocker Spaniel mutation: Substitution, PFKM gene; c.2228 G>A, p.(W473 STOP)

Wachtelhund mutation : Substitution, PFKM gene; c.550 C>T, p.(R184W)

Medical system: Metabolism, blood, renal

Breeds: American Cocker Spaniel, American Staffordshire Terrier/Amstaff, Chihuahua, English Cocker Spaniel, English Springer Spaniel, Siberian Husky, Wachtelhund / German Spaniel

Age of onset of symptoms: Young adult

Phosphofructokinase (PFK) is an essential enzyme for glycogen metabolism in red blood and muscle cells, especially during periods of intense exercise. PFK deficiency causes premature hemolysis of red blood cells and makes the animal intolerant to exercise. Affected animals have chronic anemia with acute crises of haemolysis associated with intense exercise, heat stroke, or prolonged barking. They become lethargic and weak. During a period of crisis, they have fever and their oral mucous membranes are very pale, pink, and even yellowish. They may also have brownish urine. There is no treatment at the moment.

 

References:

OMIA link: [0421-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Almodóvar-Payá A, Villarreal-Salazar M, de Luna N, et al. (2020) Preclinical research in glycogen storage diseases: A comprehensive review of current animal models. Int J Mol Sci 21:9621.  [pubmed/33348688]

Inal Gultekin G, Raj K, Lehman S, Hillström A, Giger U, et al. (2012) Missense mutation in PFKM associated with muscle-type phosphofructokinase deficiency in the Wachtelhund dog. Mol Cell Probes 26:243-7. [pubmed/22446493]

Hillstrom A, Tvedten H, Rowe A, Giger U. (2011) Hereditary Phosphofructokinase Deficiency in Wachtelhunds. J Am Anim Hosp Assoc. 47(2):145-50. [pubmed/21311071]

Gerber K, Harbey JW, D’agorne S, Wood J, Giger U (2009) Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. Vet Clin. Pathology 38(1):46-51. [pubmed/19228357]

Skibild E, Dahlgaard K, Rajpurohit Y, et al. (2001) Haemolytic anaemia and exercise intolerance due to phosphofructokinase deficiency in related springer spaniels Journal of Small Animal Practice 42:298-300.  [pubmed/11440399]

Smith BF, Stedman H, Rajpurohit Y, et al. (1996) Molecular basis of canine muscle type phosphofructokinase deficiency Journal of Biological Chemistry 271:20070-20074. [pubmed/8702726]