Medium-Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency

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Find out if your Cavalier King Charles Spaniel could develop Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency at CAGT.

Categories ,
Turnaround 1-2 weeks
OMIA OMIA002585-9615


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.

Autosomal Recessive

The frameshift indel in the gene called ACADM that causes Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in Cavalier King Charles Spaniel is autosomal recessive. This means that dogs that carry two copies of the mutation (homozygotes) will almost certainly develop MCAD Deficiency during their lives. Dogs that carry a single copy of the mutation (also known as carriers or heterozygotes) will not develop MCAD Deficiency as a result of the ACADM mutation, but they will pass the mutation onto about half of any offspring they have. Breeding dogs that will not develop MCAD Deficiency should be the breeder’s priority, with a reduction in mutation frequency within the whole breed being the secondary, longer-term target.

Carriers can be bred from safely, provided they are mated to a dog that has also been tested and is clear of the ACADM mutation (i.e. carry no copies of the mutation). If a carrier is mated to a clear dog approximately half of the resulting puppies will also be carriers, so should be tested themselves prior to breeding. Breeding carriers to tested, clear dogs is safe, in terms of avoiding dogs affected with Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, and will help to maintain the genetic diversity of a breed. It is therefore encouraged, particularly in the first few generations following the availability of a new genetic test, so that other desirable characteristics and traits can be preserved before the frequency of the disease mutation within the breed is gradually reduced.

Variant c.444_445delins; p.(Thr150Ilefs*6)
Assay Type Variant Specific
Inheritance Autosomal Recessive
Severity Moderate: Affected animals experience significant discomfort or dysfunction, management/treatment costs may be relatively high and life expectancy can be reduced.

Christen M, J Bongers, D Mathis et al. (2022) ACADM Frameshift Variant in Cavalier King Charles Spaniels with Medium-Chain Acyl-CoA Dehydrogenase Deficiency. Genes. 13(10): 1847 . DOI: 10.3390/genes13101847.