Laboratory diagnosis of MH susceptibility

Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disease triggered by commonly used volatile anaesthetics and/or succinylcholine (1). In vitro muscle contracture testing (IVCT) is the gold standard test to establish an individual's risk of MH susceptibility. The European MH Group has elaborated a standardized protocol for IVCT (2,3) and has initiated international collaborative molecular genetic studies to investigate the molecular basis of MH. Data from these studies demonstrate that MH has a high level of locus heterogeneity. Thus, the diagnosis of MH susceptibility cannot be made using a simple genetic test (1). It is important to avoid false MH negative (MHN) diagnoses because of the potential risk of MH during general anaesthesia for these patients and their offspring. However, there may be situations where genetic data provide additional diagnostic information or contribute information independent of IVCT. The European MH Group has published recently guidelines for molecular genetic detection of susceptibility to MH to outline recommended procedures for the potential diagnostic use of genetic findings depending on the different clinical situations that may arise (4). The diagnostic guidelines are regularly updated by the European MH Group and published on this website.

The usual route of entry for individuals into MH investigations follows a suspected MH crisis and referral of the patient to an MH Investigation Unit. The diagnostic procedures and genetic counselling are performed according to current knowledge.

References:

1.) Denborough M. Malignant hyperthermia. Lancet 1998; 352: 1131-36.
2.) European MH Group. A protocol for the investigation of malignant hyperpyrexia (MH) susceptibility. Br J Anaesth 1984; 56: 1267-9.
3.) Ording H for the European Malignant Hyperthermia Group. In vitro contracture test for the diagnosis of malingant hyperthermia following the protocol of the European MH Group: Results of testing patients surviving fulminant MH and unrelated low-risk subjects. Acta Anaesthesiol Scand 1997; 41: 955-66.
4.) Urwyler A, Deufel T, McCarthy T, West S for the European Malignant Hyperthermia Group. Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Br J Anaesth 2001; 86: 283-7.

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