Test Detail
MCAD deficiency - Cavalier King Charles Spaniel
Metabólico · Dog
Inborn error of fatty acid beta-oxidation due to medium-chain acyl-CoA dehydrogenase deficiency (ACADM/MCAD). It prevents the energetic use of fatty acids during fasting or exertion, producing hypoketotic hypoglycemia with acidosis and a risk of collapse or sudden death. It has been described in the Cavalier King Charles Spaniel and is inherited in a recessive manner.
Incidence
Specific to the Cavalier King Charles Spaniel. In genotyping of 162 additional CKCS the variant allele frequency was 23.5%, with 12 additional mutant homozygotes (Christen et al. 2022, PMID 36292732); the variant was not found in 923 control genomes from other breeds.
Breeder management
- Test breeding animals before mating
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; test offspring intended for breeding
- Avoid spreading the allele to lines where it does not exist
- In known homozygotes, avoid prolonged fasting and manage exercise
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier can be mated to a clear animal; test offspring intended for breeding
- Avoid spreading the allele to lines where it does not exist
- In known homozygotes, avoid prolonged fasting and manage exercise
Specialist notes
Differential diagnosis with other causes of collapse and sudden death in the Cavalier (degenerative mitral valve disease, syncopal collapse, epilepsy) and with other beta-oxidation errors. Laboratory findings of hypoketotic hypoglycemia and the acylcarnitine profile are suggestive; the genetic test confirms carrier status. Management of homozygotes includes avoiding fasting and offering frequent carbohydrate-rich meals.
References
1. Christen M, Bongers J, Mathis D, Jagannathan V, Quintana RG, Leeb T. (2022) ACADM Frameshift Variant in Cavalier King Charles Spaniels with Medium-Chain Acyl-CoA Dehydrogenase Deficiency. Genes (Basel) 13:1847. PMID: 36292732