That MH occurs during anesthesia and even today may lead to death and permanent or temporary disability is certainly true. What we now realize is that MH should be considered not as just a problem of anesthesia but as a medical disorder like other disorders. To make this point, consider another inherited disorder, sickle cell disease. This condition is due to a specific genetic change that leads to a deformity of the patientâ??s red blood cells. In the mildest form (the heterozygote, i.e. where only one abnormal gene is inherited) patients may be asymptomatic. However, under certain circumstances the patient may experience significant problems. For example, at high altitude they may develop extreme bone and joint pain. In addition, these individuals seem to be more prone to developing infections than patients who do not have the trait. The same analogy may be made to MH, but in this case anesthetic drugs are the â??environmentalâ?? change that leads to problems.
Moreover, in addition to issues related to certain anesthetics, some MH patients develop muscle breakdown with exercise. A few may even experience a lethal MH event when overheated. I must remind the reader that it is the rare MH patient that experiences such problems (we believe). We currently do not know how to identify which MH susceptibles are at risk of developing problems without exposure to anesthesia.
These problems should not really surprise us, because MH is a myopathy; that is, a pathologic change in muscle. There are scores of myopathies or muscle diseases, some with predictable dire consequences such as muscular dystrophy, while others are annoying and somewhat restrictive but compatible with a normal life. All the myopathies, MH included, have as their basis a change or set of changes in DNA which leads to abnormal protein structure and function of the muscle. This is certainly true of MH. The DNA changes in MH lead to an abnormal structure of an important regulator protein (or proteins) that controls calcium movements and concentrations within the muscle cell. Calcium levels in the cell â??turn onâ?? or â??turn offâ?? muscle contraction as well as energy production. We know that there are at least two regulatory proteins that are affected, the dihydropyridine receptor (DHPR) and the ryanodine receptor (RYR). Some studies indicate that there are other calcium regulatory proteins in muscle that when absent or deformed may also lead to the pathophysiologic changes of MH.
As with many other inherited disorders, the study of the basic abnormality that gives rise to MH has provided insight into how normal muscle functions and what all those proteins in muscle actually do.
Also, animals with DNA changes that are known to cause MH in humans will experience MH signs. For example, the genetically engineered mouse model of MH (that is, the insertion of an MH mutation into a normal mouseâ??s DNA) is providing insights into the clinical manifestations of MH. For example, these animals regularly develop MH not only on exposure to anesthetics but also on exposure to heat.
Patients with MH susceptibility, like patients with any other disorder, need special care and advice from physicians, nurses, genetic counselors, and others who are familiar with the disorder. MH patients have questions related to anesthesia, fitness for military service, inheritance of the disorder, problems with other medications, and most problematic, participation in sports or exposure to extreme heat. Furthermore when an MH susceptible travels abroad they have questions about what preparation should be made in regard to their MH susceptibility. Many large countries, such as China do not have dantrolene readily available. We hear of deaths or near misses from MH in countries such as the Philippines, Peru to name just a few, because dantrolene is not available.
The point of this commentary is to explain that MH is not just an adverse reaction to anesthesia - - just avoid the anesthetic triggers and you will be fine. That does not tell the whole story. There is much more to learn about MH and its implications. To put this in perspective, genetic studies show that as many as one in 3,000 people have one of the known DNA changes that are causal for MH. I believe that there are many issues that are associated with this inherited disorder of skeletal muscle that we have yet to learn about.