Medical News: Anesthesiology: New Mutation Linked to Malignant Hyperthermia

The finding may make it easier to develop a blood test for susceptibility to the condition, replacing current invasive tests, according to Lukas Georg Weigl, Ph.D., and colleagues at the Medical University of Vienna.

The mutation in the gene for ryanodine receptor one (RYR1) was found in members of an Austrian family, some of whose members are susceptible to malignant hyperthermia, Dr. Weigl and colleagues said in the September issue of Anesthesiology.

More than 170 mutations in the RYR1 gene are known to be linked to malignant hyperthermia, as is at least one outside the gene. But developing a blood test requires knowing most if not all variants, Dr. Weigl said in a statement.

"Proving the causative role of a new mutation enables researchers to include it in the list of (malignant hyperthermia) mutations and makes the genetic test more reliable," Dr. Weigl said. 

The finding may make it easier to develop a blood test for susceptibility to the condition, replacing current invasive tests, according to Lukas Georg Weigl, Ph.D., and colleagues at the Medical University of Vienna.

The mutation in the gene for ryanodine receptor one (RYR1) was found in members of an Austrian family, some of whose members are susceptible to malignant hyperthermia, Dr. Weigl and colleagues said in the September issue of Anesthesiology.

More than 170 mutations in the RYR1 gene are known to be linked to malignant hyperthermia, as is at least one outside the gene. But developing a blood test requires knowing most if not all variants, Dr. Weigl said in a statement.

"Proving the causative role of a new mutation enables researchers to include it in the list of (malignant hyperthermia) mutations and makes the genetic test more reliable," Dr. Weigl said.

This is an important step toward establishing an inexpensive and minimally invasive genetic test," he said.

Malignant hyperthermia, an inherited condition, is hard to identify before exposure to a triggering anesthetic, which usually occurs during a surgical procedure.

The effects include increased temperature and muscle rigidity, leading to muscle damage and release of ions and proteins into the blood. That in turn can lead to death from cardiac dysrhythmias or kidney damage.

The current test for susceptibility -- the in-vitro contracture test -- involves removing muscle tissue from an individual's thigh and checking it for sensitivity to caffeine and halothane, both triggering substances.

For the current study, researchers looked at a nine-member family after one of its members, a six-year-old girl, showed signs of possible malignant hyperthermia during an adenotomy.

The girl had developed tachycardia, at 252 beats per minute, masseter spasm, and mydriasis without pupillary reflexes.

Later, four family members had the muscle test and two proved to be susceptible.

The RYR1 gene was sequenced for the two susceptible members, and DNA from 100 non-family members, all confirmed negative for malignant hyperthermia, was used as a control.

Genetic analysis showed a nucleotide exchange from thymine to cytosine, in exon 87 at position 11953, which causes the amino acid tryptophan at position 3985 of the protein to change to arginine, the researchers said.

The variant -- dubbed W3985R -- was not found in nonsusceptible members of the family or in the control group.

Although the findings imply that the variant causes malignant hyperthermia, the researchers said, it can only be confirmed if the same mutation is found to be associated with the condition in another family. This is an important step toward establishing an inexpensive and minimally invasive genetic test," he said. 

The current test for susceptibility -- the in-vitro contracture test -- involves removing muscle tissue from an individual's thigh and checking it for sensitivity to caffeine and halothane, both triggering substances.

For the current study, researchers looked at a nine-member family after one of its members, a six-year-old girl, showed signs of possible malignant hyperthermia during an adenotomy.

The girl had developed tachycardia, at 252 beats per minute, masseter spasm, and mydriasis without pupillary reflexes.

Later, four family members had the muscle test and two proved to be susceptible.

The RYR1 gene was sequenced for the two susceptible members, and DNA from 100 non-family members, all confirmed negative for malignant hyperthermia, was used as a control.

Genetic analysis showed a nucleotide exchange from thymine to cytosine, in exon 87 at position 11953, which causes the amino acid tryptophan at position 3985 of the protein to change to arginine, the researchers said.

The variant -- dubbed W3985R -- was not found in nonsusceptible members of the family or in the control group.

Although the findings imply that the variant causes malignant hyperthermia, the researchers said, it can only be confirmed if the same mutation is found to be associated with the condition in another family.