Comparison of European and North American malignant hyperthermia diagnostic protocol outcomes for use in genetic studies

Background: Halothane and caffeine diagnostic protocols and an experimental ryanodine test from the North American Malignant Hyperthermia (MH) Group ( NAMHG) and the European MII Group (FMHG) have not been compared in the same persons until now. Methods: The outcomes of the NAMHG and EMHG halothane and caffeine contract ure tests were compared in 84 persons referred for diagnostic testing. In a ddition, the authors assessed the experimental ryanodine protocol in 50 of these persons. Results: Although the NAMHG and EMHG halothane protocols are slightly diffe rent methodologically, each yielded outcomes in close (84-100%) agreement w ith diagnoses made by the other protocol. Excluding 23 persons judged to be equivocal (marginally positive responders) by the EMHG protocol resulted i n fewer persons classified as normal and MH susceptible (42 and 19, respect ively) than those classified by the NAMHG protocol (48 and 34, respectively ). For the G1 persons not excluded as equivocal, the diagnoses were identic al by both protocols, with the exception of one person who was diagnosed as MII susceptible by the NAMHG protocol and as "normal" by the EMHG protocol . The NAMHG protocol produced only mo equivocal diagnoses. Therefore, a nor mal or MH diagnosis by the NAMHG protocol was frequently associated with an equivocal diagnosis by the EMHG protocol. The time to 0.2-g contracture af ter the addition of 1 mu M ryanodine completely separated populations, whic h was in agreement with the EMHG protocol and, except for one person, with the NAMHG protocol. Conclusions: Overall, the NAMHG and EMHG protocols and the experimental rya nodine test yielded similar diagnoses. The EMI-IG protocol reduced the numb er of marginal responders in the final analysis, which may make the remaini ng diagnoses slightly more accurate for use in genetic studies.