Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a fatty-acid oxidation disorder. A genetic form of the disease has been reported in Cavalier King Charles Spaniels. MCAD usually mediates the oxidation of medium-chain fatty acids, which provides energy to the body during periods of stress or fasting. A deficiency of MCAD results in the accumulation of medium-chain fatty acids and the inability to produce sufficient energy during periods of stress. Affected dogs present with clinical signs that include prolonged lethargy, being less responsive and proprioceptive ataxia (wobbliness and abnormal stance and gait). Episodes can last for 20 minutes to multiple hours. While the disease can result in coma and even death, it can also me managed successfully with medication and dietary and lifestyle changes, especially if diagnosed early.
The genetic variant identified is common in the breed, with an allele frequency of approximately 23.5%. Approximately 7% of dogs tested were affected (homozygous) and 32% were carriers of the variant. The disease in affected dogs does not appear to be as clinically severe as it is in humans, which suggests additional compensatory mechanisms in the dog.