Overview

• Phosphofructokinase is the most important rate-controlling enzyme in glycolysis, and RBCs and intensely exercising skeletal muscles depend heavily on anaerobic glycolysis for energy.
• Affected dogs have compensated hemolytic anemia and generally mild myopathy caused by markedly reduced total phosphofructokinase activity in both tissues.
• Anemia develops because of insufficient generation of ATP to maintain normal RBC shape, ionic composition, and deformability and because RBCs from affected dogs are alkaline fragile and lyse when blood pH is slightly high.

Signalment

• English springer spaniel, American cocker spaniel, mixed breed, whippet, and wachtelhund dogs.
• Transmitted as an autosomal recessive trait.
• Affected homozygous animals generally not recognized as abnormal before 1 year of age.

Signs

• Some animals exhibit mild clinical signs that go unrecognized for years; others regularly exhibit episodes of severe illness.
• Depression or weakness concomitant with episodes of red to brown pigmenturia; hemoglobinuria less likely to be recognized in female dogs, because of the sex difference in urination pattern.
• Mild lethargy with slight fever during mild hemolytic episodes.
• Marked lethargy, weakness, pale or icteric mucous membranes, mild hepatosplenomegaly, muscle wasting, and fever as high as 41°C (106°F) possible during severe hemolytic crises.
• Intravascular hemolysis can be caused by hyperventilation-induced alkalemia associated with exercise or excitement.
• Signs of muscle dysfunction-usually limited to exercise intolerance and slightly diminished muscle mass, but muscle cramping and severe progressive myopathy can occur.
• Two affected whippets had progressive cardiac disease in addition to muscle cramping after exercise.
• Heterozygous carrier animals appear clinically normal.

Causes & Risk Factors

Deficiency of the muscle-type subunit of phosphofructokinase-markedly reduced total activity in RBCs and skeletal muscle.

Differential Diagnosis

• Other causes of hemolytic anemia-immune-mediated hemolytic anemia, hemotrophic mycoplasmosis, babesiosis, Heinz body hemolytic anemia, microangiopathic hemolytic anemia, and pyruvate kinase deficiency.
• Affected dogs-negative Coombs' test, no parasites or Heinz bodies in stained blood films, seronegative for Babesia spp., and no evidence of DIC or heartworm disease.
• Differentiated from pyruvate kinase deficiency by specific enzyme assays or DNA test.

CBC/Biochemistry/Urinalysis

• Persistent compensated hemolytic anemia.
• MCV usually 80–90 fL.
• Reticulocyte counts generally 10–30%.
• HCT values generally 30–40%; during hemolytic crises may decrease to 15%.
• Bilirubinuria-often markedly high in male dogs.
• Hemoglobinuria in association with episodes of intravascular hemolysis.
• Serum-slightly high potassium, magnesium, calcium, urea, AST, total protein, and globulin; slightly to moderately high LDH, ALP, iron, and bilirubin; markedly high bilirubin in association with a hemolytic crisis; markedly high urea and creatinine if renal failure develops secondary to hemoglobin nephrosis or shock.

Other Laboratory Tests

• Measure RBC phosphofructokinase activity-easily identify affected animals older than 3 months; heterozygous carrier dogs have approximately one-half normal activity.
• Perform DNA test by PCR technology-clearly differentiate normal and carrier animals of any age. Wachtelhund dogs have a genetic mutation that is different from the defect in the other dog breeds.

Drug(s)

For fever that often accompanies intravascular hemolysis and potentiates hemolytic crisis-aspirin (10 mg/kg PO q12h) or dipyrone (0.055 mL of 50% solution/kg SC q8h).

Abbreviations

• ALP = alkaline phosphatase
• AST = aspartate aminotransferase
• ATP = adenosine triphosphate
• DIC = disseminated intravascular coagulation
• HCT = hematocrit
• LDH = lactate dehydrogenase
• MCV = mean cell volume
• PCR = polymerase chain reaction
• RBC = red blood cell

Internet Resources

• http://research.vet.upenn.edu/penngen.