Last updated 2mo ago
During anesthesia for routine surgery, a 25-year-old develops rapidly rising temperature, muscle rigidity, hypercarbia, and metabolic acidosis. The anesthesiologist stops the triggering agents and administers dantrolene.
AD; RYR1 (most common), CACNA1S.
- RYR1 encodes the ryanodine receptor (calcium release channel) on the sarcoplasmic reticulum in muscle cells
- CACNA1S encodes the alpha-1 subunit of the L-type voltage-gated calcium channel on muscle cell membranes
- Normal muscle contraction: nerve signal → CACNA1S opens → triggers RYR1 to release calcium from sarcoplasmic reticulum → muscle contracts
- In MH: Mutations cause abnormal calcium regulation. Triggering agents (volatile anesthetics, succinylcholine) cause uncontrolled calcium release → sustained muscle contraction → heat production, metabolic crisis
- Dantrolene works by blocking RYR1, stopping the excessive calcium release
- Triggered by volatile anesthetics (halothane, sevoflurane) and succinylcholine
- Hyperthermia, muscle rigidity
- Hypercarbia, metabolic acidosis
- Rhabdomyolysis (elevated CK), hyperkalemia
- Can be fatal without treatment
Testing: Muscle contracture test (caffeine-halothane); genetic testing
- Acute crisis is a clinical diagnosis: hypercarbia, hyperthermia, rigidity, tachycardia, and metabolic/respiratory acidosis after a triggering agent; elevated CK and hyperkalemia support it
- Caffeine-halothane (in vitro) contracture test on fresh muscle biopsy is the gold standard for susceptibility
- Molecular testing of RYR1 and CACNA1S confirms susceptibility and enables targeted family testing
- Susceptibility is often identified after an index event or a positive family history; counsel relatives and offer cascade testing
- Dantrolene (reverses calcium release), supportive care
"CentRal coRe disease = Ryanodine Receptor RYR1": RYR1 variants cause both malignant hyperthermia susceptibility and central core disease (a congenital myopathy). The "R" pattern in "centRal coRe" points to the Ryanodine Receptor.
"EYE of the storm = RYR1": The "RY" in RYR looks like an eye, and the storm represents the metabolic crisis triggered by anesthetics.
"Overheat": Malignant hyperthermia = uncontrolled calcium release causing sustained muscle contraction and dangerous heat production.