Malignant Hyperthermia

How Common is MH?

MH reactions are uncommon, occurring in between 1 in 30,000 to 1 in 200,000 general anaesthetics. The incidence is highest in children and teenagers and is more common in males rather than females. We do not understand the reasons for this age and sex distribution of reactions.

We also know that people who have the MH genetic defect do not have an MH reaction on every occasion that they receive triggering drugs. We do not fully understand why this happens. However, it is important to know that someone who has had an uncomplicated general anaesthetic before, may still be at risk of developing MH during a subsequent anaesthetic.

Based on the number of MH reactions in the UK and the number of general anaesthetics given in the country, we estimate the genetic defect to be present in just under 1 in 10,000 of the population.

Causes

The drugs that cause the MH reaction are the most commonly used drugs for keeping somebody asleep during an anaesthetic.

These are the anaesthetic gases that include isoflurane, sevoflurane, desflurane, enflurane, methoxyflurane and halothane. These are all chemically related to the original anaesthetics ether and chloroform.

Another drug involved in the triggering of malignant hyperthermia is suxamethonium. There is controversy whether suxamethonium alone can trigger a full MH reaction. However, in MH patients it can cause muscle rigidity, muscle necrosis or breakdown and can cause a more florid and rapidly progressive MH reaction in combination with one of the inhalational anaesthetic triggers.

Genetics

All of our physical characteristics are determined by our genes. Each gene carries a code that is used to make a unique protein. We each have two copies of every gene, one inherited from our mother and the other from our father. The only exception to this is the genes that are present on our sex chromosomes. As far as we know, the genetic defects responsible for malignant hyperthermia are not located on the sex chromosomes.

When a fault or change occurs in a gene, the effect of the change will depend on the nature of the gene change and the protein encoded by the gene. In many instances a gene change in one out of the two copies of the gene will not have any noticeable effect. Some genetic disorders, however, require only one of the two copies to be affected by a gene change for the genetic disorder to be apparent. Such a genetic disorder is called a dominant condition because the one gene change affects the function of the protein encoded by the gene.

In most MH families, MH susceptibility appears to be inherited in a dominant fashion. However, in at least 10% of MH families the inheritance of MH susceptibility can only be explained by the presence of more than one gene change. This could be a result of more than one gene change in a single gene or gene changes in more than one gene. This situation is by no means unique to MH, with several other apparently simple genetic disorders being influenced by changes in more than one gene.

To date, the most commonly implicated gene associated with MH is called the RYR1 gene. This gene encodes a protein that is only made in skeletal muscle tissue where it has a major role in controlling the calcium release within the muscle cell. Many gene changes in the RYR1 gene have been found but only a minority of these have been shown to cause an MH response. Indeed, there are several gene changes in the RYR1 gene that have been found in people who are not susceptible to MH. Two other genes have been implicated in MH susceptibility but their involvement is rare, affecting less than 1% of MH cases. In approximately 30% of MH cases RYR1 and the two other known genes have been excluded as the cause of MH susceptibility.

Diagnostic Testing

It is really important that anyone who has suspected MH undergoes testing. This is because it could be a life-threatening condition for a patient’s relatives as well as themselves. The more we research and learn about existing MH patients, the more likely we will help future sufferers.

There are two types of test to confirm MH. These are:

1. Genetic screening (blood test)
2. Muscle biopsy

Genetic screening

Genetic screening via a blood test may be offered as the initial test to a person who has had a suspected MH reaction. If a gene change known to cause MH is found in the blood sample then MH will be confirmed, and no further testing will be needed. However, a large number of MH patients (c. 60-65%) do not necessarily have an identifiable gene change and would need to undergo further testing using the muscle biopsy. Where a gene change is found in the family, genetic screening can initially be used in other family members.

In those cases who are put forward for genetic screening, a blood test will be taken at a local GP practice and sent off to for screening at the specialist UK MH investigation centre in Leeds.

Muscle biopsy

Muscle biopsy testing for MH involves a two-night stay at the Leeds MH Investigation Unit at St James’s Hospital in Leeds. A sample of muscle tissue is taken through an incision in the lower thigh (c. 2-2.5 inches). The procedure is done under local anaesthetic and takes 30 to 40 minutes to be done.

Testing Family Members

MH is an inherited condition and once it has been found in a family testing will also be offered to other family members, to see if they are at risk. This is done in a systematic way where the closest relatives are tested first.

The choice of test will vary from family to family, depending on whether a gene change associated with malignant hyperthermia has been found or not. Where such a gene change has been found a positive gene test (blood sample) will define high risk for malignant hyperthermia under anaesthesia.

However because of the possibility of more than one gene change being responsible for MH in some families, a negative gene change must be confirmed by the muscle biopsy tests. It is only through the muscle biopsy tests that someone who is possibly at increased risk of MH can be shown not to be at risk.

The muscle biopsy tests can only be done in adults and children more than 10 to 12 years of age. There is also a minimum body weight for a child of 30 kg. These limitations on the muscle biopsy are principally because there is uncertainty of the accuracy of the biopsy tests in younger children. There is also some concern that the muscle biopsy may have an unacceptable cosmetic result in younger children.

Help and Support

The UK MH Registry is an online resource which has been created to give support and information on malignant hyperthermia for patients and relatives, who may have or suspect they have the condition.

The UKMHR also has essential information, resources and an emergency helpline number for anaesthetists and other health professionals, who need to be aware of how to care for an MH patient.

Please visit www.ukmhr.ac.uk
Patient helpline number: 0113 206 5270