Acyl-CoA dehydrogenase deficiency in Cavalier King Charles Spaniel

Acyl-CoA dehydrogenase is the enzyme responsible for converting fats into alternative energy sources. Its deficiency is associated with impaired processing of medium-chain fatty acids. The disease manifests itself in episodes of prolonged lethargy, proprioceptive ataxia, and complex seizures.

The cause of the disease is mutation c.444_445delinsGTTAATTCTCAATATTGTCTAAGAATTATG in the ACADM gene, encoding acyl-CoA dehydrogenase. The mutation results in introduction of the premature stop codon and truncation of the resulting protein, which is non-functional. It is a relatively widespread disease in the breed. A study in 2022 revealed a mutation frequency of 23.5% of heterozygous dogs and 12 additional homozygous mutant dogs.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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Reference:

Christen, M., Bongers, J., Mathis, D., Jagannathan, V., Quintana, R.G., Leeb, T. : ACADM frameshift variant in Cavalier King Charles Spaniels with medium-chain acyl-CoA dehydrogenase deficiency. Genes (Basel) 13, 2022. Pubmed reference: 36292732