Inherited defect of glycolysis due to deficiency of the muscle subunit of phosphofructokinase (PFKM). It causes exercise intolerance with haemolytic crises and myopathy, and favours haemolysis with the appearance of echinocytes on the blood smear. Crises are usually triggered by intense exercise, excitement or alkalotic hyperventilation. It is inherited in a recessive manner.

Specific to the English springer spaniel, the American cocker spaniel, the German spaniel (Deutscher Wachtelhund) and the whippet. No reliable carrier figures are published for the overall population; in the springer spaniel it is considered relatively uncommon today thanks to breeding control.

- Exercise intolerance with crises after exertion or excitement
- Haemolytic anaemia with jaundice and haemoglobinuria
- Myopathy with weakness and muscle cramps
- Echinocyte bodies on blood smear
- Muscle spasms and stiffness after exercise
- Improvement with rest

PFKM deficiency was initially characterised in the English springer spaniel as the breed's myopathy with haemolytic anaemia; the PFKM nonsense variant (c.2228G>A) is identical in the English springer spaniel, the American cocker spaniel and the whippet (Smith et al., 1996). A distinct missense variant was later described in the Deutscher Wachtelhund (Inal Gultekin et al., 2012). The availability of a genetic test now allows carrier control in breeding.

- Test breeding animals before mating
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier may be mated to a clear animal; test the offspring intended for breeding
- Do not mate lines of different breeds carrying similar variants to each other without testing
- Avoid spreading the allele to lines where it does not exist

Differential diagnosis with other exertional myopathies (MCD, PDP1 and pyruvate kinase deficiency) and with immune haemolytic anaemias. The crisis is due to haemolysis with echinocytosis after hyperventilatory alkalosis; the smear is informative. The genetic test confirms carriers; variants vary with breed, so the appropriate test should be used for each.

1. Smith BF et al. 1996. Molecular basis of canine muscle type phosphofructokinase deficiency. J Biol Chem. PMID: 8702726
2. Gerber K et al. 2009. Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets. Vet Clin Pathol. PMID: 19228357
3. Hillström A et al. 2011. Hereditary phosphofructokinase deficiency in wachtelhunds. J Am Anim Hosp Assoc. PMID: 21311071
4. Inal Gultekin G et al. 2012. Missense mutation in PFKM associated with muscle-type phosphofructokinase deficiency in the Wachtelhund dog. Mol Cell Probes. PMID: 22446493