Phosphofructokinase deficiency

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Blood smear (using Methylene blue stain) from a PFK-affected Wachtelhund showing a marked reticulocytosis[1]

Phosphofructokinase deficiency (PFK) is a genetic disease of dogs characterized by intermittent hemolytic anemia and exertional myopathy.

The disease occurs frequently in English Springer Spaniel, American Cocker Spaniel, Whippet[2] and Wachtelhund[1] and is caused by a single nonsense mutation in the PFKM gene[3].

PFK results in a glycolytic block leading to reduced ATP and 2,3-diphosphoglycerate (DPG) concentrations[4]. This leads to elevated hemoglobin-oxygen affinity and tissue hypoxia, which acts as a persistent stimulus for increased erythropoiesis even when the HCT is normal[5].

In addition to persistent compensated hemolytic anemia, PFK-deficient dogs (but not humans) may have episodes of intravascular hemolysis following periods of hyperventilation-induced alkalemia due to low DPG concentrations[6].

In PFK dogs, the hemolytic crises is typically initiated by strenuous exercise, barking, heat or excessive panting.

Clinically affected dogs present with acute exercise intolerance, exertional myopathy muscle stiffness, pale and sometimes icteric mucus membranes and a mild systolic heart murmur. Urinalysis often shows a prominent hemoglobinuria.

Blood tests commonly reveal a severe, persistent reticulocytosis, metarubricytosis, anemia, elevated creatinine kinase levels and and metabolic alkalosis.

Diagnosis is established by finding a marked reduction in erythrocyte PFK activity (often less than 1 IU/g Hb; normal = 5 - 20 IU/g Hb).

DNA testing is available for the English Springer Spaniel and American Cocker Spaniel breeds[7].

A differential diagnosis includes immune-mediated hemolytic anemia, splenic torsion, pyruvate kinase deficiency and hereditary osmotic fragility.

Acute cases may require supportive IV therapy, cage rest and immunosuppressive drugs such as prednisolone and azathioprine.

Reduction of stress and exercise restriction often allows affected dogs to lead a normal life.

References

  1. 1.0 1.1 Hillström A et al (2011) Hereditary phosphofructokinase deficiency in wachtelhunds. J Am Anim Hosp Assoc 47(2):145-150
  2. Gerber K et al (2009) Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. Vet Clin Pathol 38(1):46-51
  3. 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
  4. Harvey JW et al (1992) Characterization of phosphofructokinase-deficient canine erythrocytes. J Inherit Metab Dis 15:747–759
  5. Giger U et al (1986) Autosomal recessive inherited phosphofructokinase deficiency in English Springer spaniels. Anim Genet 17:15–23
  6. Harvey JW et al (1988) Effect of 2,3-diphosphoglycerate concentration on the alkaline fragility of phosphofructokinase-deficient canine erythrocytes. Comp Biochem Physiol B 89B:105–109
  7. Gerber K et al (2009) Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. Vet Clin Pathol 38(1):46–51