Testing of dogs: Malignant Hyperthermia

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Usual turnaround time: 7 business days
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MH - Malignant Hyperthermia, test for all breeds

Malignant hyperthermia (MH) is a severe complication during the general anaesthesia that can be even fatal. MH is a pharmacogenetic disease of skeletal muscles characterized by hypercapnia, tachycardia and hyperthermia, which occur in response to some chemical drugs, in this case anaesthetics. The affected dogs have no clinical symptoms unless they are exposed to these drugs inducing this condition. Malignant hyperthermia was described in people and various animal kinds (e.g. cats, dogs, horses, cattle and rabbits).

In dogs, the C >T-substitution was found as the causative mutation leading to substitution of the valine to alanine amino acids at position 547 (p.Val547Ala). This mutation was found in a highly conserved gene region of the ryanodine receptor (RYR1 gen) (Roberts et al. 2001). Ryanodine receptor is a part of a calcium-releasing channel in the sarcoplasmic reticulum. If the mutation is present in the receptor, an uncontrolled release of calcium ions Ca2+  from the sarcoplasmic reticulum is triggered after exposure to the trigger substance in connection with impaired reabsorbing of excess calcium ions. It causes a prolonged muscle contraction without relaxation and the effort to reabsorb the calcium ions results in extreme O2 consumption, over production of CO2 and heat generation (hyperthermia).

Dogs with malignant hyperthermia are healthy without clinical signs unless they are exposed to the trigger substances.  In case of general anaesthesia, hypercapnia, tachycardia and hyperthermia occur. If the anaesthesia is not interrupted, the signs may develop in arrhythmia, rhabdomyolysis, renal failure and death. The trigger substances are common volatile and gaseous inhalational anaesthetic agents (e.g. halothane, isoflurane and sevoflurane) and non-polarising muscle relaxants such as succinylcholine (Roberts et al. 2001, Brunson et al. 2004).

The treatment shall start with interruption of the anaesthesia, cooling the organism and administration of antidotes reducing the muscle tension, e.g. dantrolene.  For dogs affected with MH, alternative anaesthetics can be applied and the pre-medication is also very important as the stress can be a factor contributing to the development of clinical signs   (Brunson et al. 2004).

The MH is inherited as an autosomal dominant disorder. Only one copy of the mutated gene is sufficient for development of clinical signs. Mutation is not bound to specific breeds (Brunson et al. 2004.)  With regard to the fact that affected animals are without clinical signs, provided they are not exposed to the trigger substance,  some animals can live their whole life without diagnosing the disposition for MH. In case of affected animal the risk of transfer to the offsprings is 50%.

References:
Roberts, M.C., Mickelson, J.R., Patterson, E.E., Nelson, T.E., Armstrong, P.J., Brunson, D.B., Hogan, K. : Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1) Anesthesiology 95:716-725, 2001. Pubmed reference: 11575546.
Brunson, DB., Hogan, KJ. : Malignant hyperthermia: a syndrome not a disease. Vet Clin North Am Small Anim Pract 34:1419-33, 2004. Pubmed reference: 15474681. DOI:10.1016/j.cvsm.2004.05.010.

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Usual turnaround time: 7 business days
1 test price: 54.00 $ without VAT