Inborn error of energy metabolism due to a deficiency of pyruvate dehydrogenase complex phosphatase 1 (PDP1). It prevents activation of the pyruvate dehydrogenase complex, which impairs the entry of pyruvate into the Krebs cycle and produces lactic acidosis with exercise. Affected dogs show exercise intolerance and post-exercise collapse. It is inherited in a recessive manner.

Specific to the Clumber Spaniel and the Sussex Spaniel, breeds with small numbers. No reliable carrier frequencies are published for the general population; the inbreeding typical of both breeds favours concentration of the allele.

- Marked exercise intolerance\n- Post-exercise collapse with recovery after rest\n- Lactic acidosis after exertion\n- Muscle weakness after intense activity\n- No signs at rest

PDP1 deficiency was described in the Clumber Spaniel and the Sussex Spaniel after investigation of cases of exercise intolerance and lactic acidosis. Molecular studies associated it with a variant of the PDP1 gene that reduces phosphatase activity, keeping the pyruvate dehydrogenase complex in its phosphorylated and inactive form. This characterization enabled a genetic carrier test for both breeds.

- Test breeders before mating\n- Do not cross two carriers: 25 % risk of affected homozygotes\n- A carrier may be crossed with a clear dog; test the offspring intended for breeding\n- Avoid spreading the allele to lines where it is not present\n- In breeds with small numbers, prioritize genetic diversity when replacing carriers

Differential diagnosis with other causes of post-exercise collapse (exercise-induced collapse syndrome EIC, MCD deficiency, PFK deficiency, exertional myopathy) and with cardiogenic or neurological collapses. Lactic acidosis after exertion points to it; the genetic test confirms carrier status. There is no curative treatment; management is to avoid intense exercise.

1. Cameron JM et al. 2007. Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. Mol Genet Metab 90:15-23. PMID: 17095275
2. Abramson CJ et al. 2004. Pyruvate dehydrogenase deficiency in a Sussex spaniel. J Small Anim Pract 45:162-165. PMID: 15049576
3. OMIA:001406-9615 - Pyruvate dehydrogenase deficiency. https://omia.org/OMIA001406/9615/