Pyruvate Dehydrogenase Complex Deficiency
Pyruvate dehydrogenase complex deficiency (PDCD) is an inherited metabolic disorder associated with the citric acid cycle. It is caused by deficient enzyme activity in the pyruvate dehydrogenase complex, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. It is one of the most common neurodegenerative disorders associated with abnormal cellular metabolism. The citric acid cycle is a major biochemical process that derives energy from carbohydrates. Malfunction of this cycle deprives the body of energy. Because of a lack of energy during neural development, severe enzyme deficiencies may lead to congenital brain malformation. An abnormal lactate buildup results in severe lethargy, poor feeding, abnormally rapid breathing, especially during times of illness, or exertion. The disease has been reported in Old English Sheepdogs, Clumber Spaniels, and Sussex Spaniels.
Signs and Treatment
Progressive neurological symptoms usually start early in life, but may be evident at birth. These signs may include developmental delay, intermittent lack of muscle coordination, poor muscle tone, abnormal eye movements, seizures, exercise intolerance and post-exercise collapse. The mode of inheritance is autosomal recessive, therefore a dog must have two copies of the PDP1 deficiency form of the gene to show symptoms. Dogs with one copy of the PDP1 deficiency form of the gene and one copy of the normal form do not show symptoms but can pass the PDP1 deficiency form of the gene onto their puppies. Treatment of affected dogs with a high-fat, ketogenic diet has been suggested. Since the underlying progressive neurological damage is irreversible, the prognosis is usually poor.
- DNA Test for PDP1 deficiency in Clumber and Sussex Spaniels.
- Anatoly Ruvinsky, Jeff Sampson. The Genetics of the Dog.