A new DNA test may make it much simpler to identify patients atrisk of malignant hyperthermia (MH) a rare but life-threateningcomplication of exposure to common anesthetics reports the Novemberissue of Anesthesia & Analgesia, official journal of theInternational Anesthesia Research Society (IARS). The new technique, called high resolution melting (HRM) curveanalysis, provides a “sensitive and specific tool” for theidentification of genetic variants responsible for MH and a muchsimpler alternative to currently available tests. Dr Marcus Bromanof Sk ne University Hospital Lund, Malm , Sweden, is leadauthor of the new study. HRM Curve Analysis Assesses MH Risk by Measuring DNA ‘MeltingPoint’ Malignant hyperthermia is a rare condition in which geneticallysusceptible people develop rapid increases in body temperature andmuscle rigidity in response to certain anesthetics and other drugs.Once the condition is recognized, it can generally be avoided bysubstituting other anesthetics.
However, susceptible patientsgenerally go unrecognized until they (or a family member)experience an episode of MH. HRM curve analysis was developed to meet the need for a new testfor assessing MH risk. The current test is highly invasive,requiring a biopsy specimen of quadriceps (thigh) muscle andspecialized testing equipment. A genetic test would be a valuablealternative, but is impractical because so many different genevariants can cause MH. Many of them occur in a gene called RYR1 thevery large size of which makes it difficult to screen for variants.
The new test takes a different approach, using a sample of DNAextracted from a blood sample. Fragments of DNA from the RYR1 geneare identified and gradually heated to assess the temperature atwhich the strands of DNA begin to unwind. Fragments with unusual,or “aberrant,” melting profiles can undergo full gene sequencing topinpoint specific variants potentially causing MH. Dr. ISDB-T Receiver
Broman and colleagues evaluated the HRM curve analysis approachin 16 “MH susceptible” patients. All had either experienced alife-threatening episode of MH themselves, had a close relative whohad died of MH, or had undergone the muscle biopsy test forsuspected abnormalities. A total of approximately 2,500 DNAfragments underwent HRM curve analysis. The test showed “significantly aberrant melting profiles” in 21percent of the DNA fragments tested. STB Receiver Manufacturer
Subsequent gene sequencingstudies identified 131 variants known to cause MH, along with 17known or suspected mutations. Overall, 13 of the 16 MH-susceptible patients had geneticabnormalities known or suspected of causing MH a rate of 81percent. Using HRM curve analysis to look for MH-related mutationsof the RYR1 gene would greatly reduce the need for in-depth genesequencing studies, without sacrificing test sensitivity. “Thissuggests savings of both workload and cost, because technically thesequencing procedure is more laborious and expensive than the HRMprocedure,” according to Broman and coauthors. China DVB-C Digital Receiver
Although it has some limitations, HRM curve analysis is a promisingapproach to identifying patients at risk of MH, according to anaccompanying editorial by Dr Henry Rosenberg of Saint BarnabasMedical Center, Livingston, N.J. He writes, “The study, ifconfirmed and expanded by others, will greatly enhance the abilityto screen a large number of samples of DNA to facilitate furtherresearch and eventually diagnostic testing for MH susceptibility.” Dr. Rosenberg foresees a day when powerful genetic tests will beavailable to test for MH susceptibility in many different genessimultaneously. He also thinks the new findings may be relevant toother muscle diseases as well as heat-related syndromes many ofwhich are also related to RYR1 gene variants. The November issue also includes a thorough update on currenttrends and issues in MH-related research and patient care.
Authoredby Sharon J. Hirshey Dirksen, PhD, and colleagues of the MalignantHyperthermia Association of the United States (MHAUS), SherburneN.Y., the article summarizes and integrates key discussions from arecent scientific meeting sponsored by MHAUS. Additional References Citations.