EIMM

EIMM (exercise induced metabolic myopathy) is a hereditary metabolic disease that results in weakness of limb and profound muscle pain during physical exercise (e.g during a hunt).

In the muscles of affected dogs, mild to moderate necrotizing myopathy with mitochondrial abnormalities and accumulation of lipid droplets inside the muscle fibres occur.  Further, the disease is characterized by increased level of creatine kinase in blood plasma that is a sign of muscle cell damage and by a rhabdomyolyse i.e. rapid breakdown of skeletal muscles resulting in release of the degradation products (mainly myoglobin) into bloodstream and subsequently into urine.  The affected dogs show dark urine during and shortly after physical exercise as a consequence of the presence of hemoglobin or erythrocytes in urine. The symptoms of this disease are usually induced by stress, where the stress situation is not only physical exertion, but also exposure to cold.

The disease affects both male and female dogs. It has been identified in German hunting Terriers. However, its occurrence in other relative breeds cannot be excluded.

The mutation causing this disorder is called ACADVL: c.1728C>A. It is a nonsense mutation of ACADVL gene encoding a very long chain acyl-CoA dehydrogenase, an enzyme that is essential for lipid metabolism. It plays a great role in fatty acid oxidation that is the main process of energy production within mitochondria.  Due to this mutation a premature stop codon is introduced thus producing a truncated protein with 80 amino acids. The enzyme function is impaired and leads to the mentioned metabolic disorders.

The discovery of this specific mutation enabled the development of the genetic test for identification of EIMM carriers. To avoid unintentional spread of this disease, it is very important to know the genotype of the breeding animals.

EIMM is inherited autosomally recessively which means that the disease develops only in those dogs who inherit mutated allele from both parents. Carriers of mutated allele (heterozygotes) are clinically healthy but transmit the mutation on their descendants. In case of mating two heterozygous dogs there is a theoretical chance that 25% of descendants will be absolutely healthy, 50% will be carriers a 25% will inherit from both parents mutated allele and therefore will be EIMM affected.

.

Reference:

Vincent Lepori, Franziska Mühlhause, Adrian C. Sewell, Vidhya Jagannathan, Nils Janzen, Marco Rosati, Filipe Miguel Maximiano Alves de Sousa, Aurélie Tschopp, Gertraud Schüpbach, Kaspar Matiasek, Andrea Tipold, Tosso Leeb and Marion Kornberg: A nonsense variant in the ACADVL gene in German Hunting Terrier dogs with exercise induced metabolic myopathy; G3 (Bethesda). 2018 May; 8(5): 1545–1554