Pyruvate Dehydrogenase Phosphatase 1 Deficiency

What is Pyruvate Dehydrogenase Phosphatase 1 Deficiency in dogs?

Pyruvate Dehydrogenase PhosphataseAs the name suggests, Pyruvate Dehydrogenase Phosphatase 1 Deficiency is a lack of production of the enzyme Pyruvate Dehydrogenase Phosphatase 1 (PDHP1). This enzyme is inside every cell in the body and is involved in converting food into energy available for the cell to use and carry out its normal function. Without this enzyme, the cells fail to perform as they should and struggle to survive for the expected lifespan of each particular cell type. As would be expected with a lack of such a vital and important enzyme, many of the body’s different systems are affected. This lack in ability to convert food into energy is very apparent during times of exercise where there is a high need for the energy. Pyruvate Dehydrogenase Phosphatase 1 Deficiency is an autosomal recessive inherited metabolic disorder.

Genetics of Pyruvate Dehydrogenase Phosphatase 1 Deficiency in dogs

The gene responsible for Pyruvate Dehydrogenase Phosphatase 1 Deficiency is the PDP1 gene. Dogs affected by Pyruvate Dehydrogenase Phosphatase 1 Deficiency have a single point mutation in this gene. Being an autosomal recessive trait, an affected dog must have 2 copies of the mutated gene to be genetically affected by the condition. This means that the affected dog must have parents that are either carriers or affected by the disease. Having one Clear parent will prevent all of their offspring from being affected, regardless of the status of the other parent.

What is the severity of Pyruvate Dehydrogenase Phosphatase 1 Deficiency in dogs?

Pyruvate Dehydrogenase Phosphatase 1 Deficiency is considered to be a disease of medium severity as there are some treatments available and treated dogs can live a relatively normal lifespan for their breed.

What are the symptoms of Pyruvate Dehydrogenase Phosphatase 1 Deficiency in dogs?

The symptoms of Pyruvate Dehydrogenase Phosphatase 1 Deficiency often present at an early age of about 3-4 months of age. Often seen as an inability to play for long periods with littermates, there is some evidence that many puppies affected by Pyruvate Dehydrogenase Phosphatase 1 Deficiency die shortly after birth or even before birth. By the affected dog’s first year of life they will display signs of an intolerance of exercise such as an inability to play for periods longer than five minutes. Other clinical symptoms may include walking slowly, resting frequently, stopping or even collapsing during periods of moderate play. As the Pyruvate Dehydrogenase Phosphatase 1 Deficiency progresses, affected dogs may show signs of lethargy, weakness and rapid breathing during exercise. Heart and lung complications may result in an early demise of affected dogs.

Diagnosis of Pyruvate Dehydrogenase Phosphatase 1 Deficiency in dogs

Diagnosing Pyruvate Dehydrogenase Phosphatase 1 Deficiency from the clinical signs alone is very difficult as a number of other metabolic diseases often present the same symptoms. Blood and urine testing can be beneficial to ruling out other possible causes, but the most definitive diagnosis will come from a DNA Disease Screen to test for the presence of the mutated PDP1 gene.

Treatment of dogs with Pyruvate Dehydrogenase Phosphatase 1 Deficiency

Unfortunately, Pyruvate Dehydrogenase Phosphatase 1 Deficiency is not metabolically reversible, so treatments are focused on treating the symptoms as well as providing dietary supplements to make up for the lack of Pyruvate Dehydrogenase Phosphatase 1 enzyme. A high-fat, ketogenic diet has been tried with varying levels of success and modifying the affected dog’s exercise regimen to only contain light, short periods of activity helps to reduce times of great stress on the body. These measures can extend both the length and quality of life for affected dogs.

References

Anatoly Ruvinsky, Jeff Sampson. The Genetics of the Dog.

Cameron JM et al (2009) Pyruvate dehydrogenase phosphatase 1 (PDP1) null mutation produces a lethal infantile phenotype. Hum Genet 125(3):319-326

Cameron JM, Maj MC, Levandovskiy V, MacKay N, Shelton GD, Robinson BH. (2007) Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. Mol Genet Metab. 90(1):15-23

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