Malignant Hyperthermia Workup

The caffeine halothane contracture test (CHCT) is the criterion standard for establishing the diagnosis of malignant hyperthermia (MH). The test is performed on freshly biopsied muscle tissue at 30 centers worldwide; one of these centers is located in Canada, and four are located in the United States.

The CHCT testing centers in North America are located at the following sites:

• Toronto General Hospital, Malignant Hyperthermia Investigation Unit, Eaton 3-323, 200 Elizabeth St,Toronto, Ontario M5G 2C4, (416) 340-3128, Sheila.riaz@uhn.on.ca
• Uniformed Services University of the Health Sciences, Bethesda, MD (Military & Civilian); Sheila M Muldoon, MD; (301) 295-3532; smuldoon@usuhs.mil
• University of California, Davis; Timothy Tautz, MD; (530) 752-7805; timothy.tautz@ucdmc.ucdavis.edu
• University of Minnesota, Minneapolis; Paul A Iaizzo, PhD; (612) 624-7912 or (612) 624-3959; iaizz001@umn.edu (for more information on this center: www.vhlab.umn.edu/mh/index.html)
• Wake Forest University, Winston-Salem, NC; Alan G Woodruff, MD; (336) 716-7447; agwoodru@wakehealth.edu

​The patient must consult the testing center and receive approval for testing, then travel to one of the testing sites. The CHCT involves extraction of 2 g of muscle, usually from the thigh. This tissue must be tested immediately after extraction; its usability for testing lasts only a few hours.

The CHCT should be considered for all those determined to be at risk for MH (eg, those with a family history or a previous possible episode). A negative CHCT result is the only way to prove that a patient is not susceptible to MH. The cost of the test is at least $5000, but it is covered by most insurance providers.

Sevoflurane has received some preliminary study as an alternative to halothane in MH testing. ^[12]

Molecular genetic testing (DNA testing) is less expensive and less invasive than the muscle contracture test. It is 25-30% sensitive and is highly specific for MH susceptibility. The DNA is extracted from cells in a blood sample.

MH is associated with more than 30 mutations, and 30% of patients with known MH have one of these mutations. RYR1 (the gene coding for the ryanodine receptor in skeletal muscle) is associated with as many as 50-60% of MH cases in families. Mutation of CACNA1S is responsible for 1% of all cases of MH susceptibility.

Many more variations remain to be discovered. When one of the more than 30 known mutations is identified, the patient is considered to be MH-susceptible. However, a negative genetic test result does not mean that a person is MH-negative. A CHCT is needed to determine MH-negative status.

Once a family member tests positive on the CHCT, the patient can undergo genetic tests, which, if yielding positive results, can be used for the rest of the family. If the family member with the positive CHCT result is positive for one of the 30-plus mutations, the remaining family members can be tested for that mutation; if test results are positive, they are determined to be MH-susceptible. Family members who do not have one of the 30-plus mutations must still be treated as MH-susceptible and should therefore undergo a CHCT.

Molecular genetic testing centers in North America are located at the following sites:

• Center for Medical Genetics, University of Pittsburgh Medical Center, Pittsburgh, PA; (800) 454-8155; http://path.upmc.edu/divisions/mdx/diagnostics.html
• Prevention Genetics, LLC, Marshfield, WI; Eric W Johnson, PhD; (715) 387-0484; www.preventiongenetics.com
• North American Malignant Hyperthermia Registry (Database) of the Malignant Hyperthermia Association of the United States (MHAUS), Department of Anesthesiology, Children’s Hospital, University of Pittsburgh, Pittsburgh, PA 15213-2583; Dr Barbara Brandon, Director; (888) 274-7899, FAX (412) 692-8658; bwb@pitt.edu

The results of MH testing should be reported to the North American Malignant Hyperthermia Registry of MHAUS to advance the understanding of the genetics of MH. Further information is available at www.mhreg.org.