[Diagnosis of malignant hyperthermia susceptibility. 1. The significance of in vitro susceptibility tests].
Molecular genetic findings indicate genetic heterogeneity in susceptibility to malignant hyperthermia (MH). At present the in vitro contracture test (IVCT) is still the most reliable diagnostic procedure for MH susceptibility. It must be performed in a standardized fashion. METHODS. We investigated 350 patients (233 children and 117 adults) using the protocol of the European MH Group for the IVCT. The test results were classified as susceptible to MH (MHS), non-susceptible to MH (MHS), non-susceptible to MH (MHN) and equivocal (MHE), with an abnormal caffeine result designated MHEc and an abnormal halothane result designated MHEh. Reasons for the IVCT were a positive family history for MH susceptibility (n = 94), a MH reaction (n = 157), creatine kinase elevation unknown aetiology (n = 53) and different neuromuscular diseases (NMD, n = 46). Physical, neurological and laboratory work-up included serum enzymes, nerve conduction studies, electromyography and muscle biopsy evaluated by different techniques. Thirty-one children and 11 adults were MHS, while 152 children and 80 adults were MHN. MHE findings were obtained in 50 children and 26 adults. While the MHS and MHN groups are diagnostically safe, the equivocal group is not, with possible false-negative or false-positive interpretation. The high number of MHE findings most probably is explained by the high proportion of patients with NMD (53% of the children, 69% of the adults). RESULTS. In a group of 18 boys with Duchenne or Becker muscular dystrophy, ranging in age from 1.5 to 24 years, the IVCT results were twice MHS, once MHE, and MHN in the remaining 15 cases. In seven other boys with Duchenne or Becker muscular dystrophy, proven by molecular techniques, there were anaesthetic complications with MH-like symptoms. After administration of trigger substances, five out of the seven suffered a cardiac arrest, two of whom died. In the surviving five boys the IVCT results were three times MHN, once MHE and once MHS. Most probably these boys suffered from effects of succinylcholine, possibly potentiated by other trigger substances. The adverse cardiac reactions are attributed to triggered rhabdomyolysis with associated hyperkalemia but not a primary hereditary disposition to MH.


CONCLUSIONS
In patients with NMD, MHS and MHE test results do not indicate a hereditary, heterogeneous disposition to MH; the majority will be caused by a secondary induced disturbance of calcium homoeostasis in the diseased muscle cells. These results do, however, indicate the following: (1) Patients with NMD exposed to trigger substances are at higher risk than the general population for MH-like episodes, including sudden death. (2) NMD therefore should be diagnosed as early as possible and patients should not be exposed to trigger substances when alternatives are at hand. (3) Diagnostic procedures in patients having suffered an MH-like episode should include IVCT and special investigations to exclude or substantiate other NMD. The work-up may be changed if a family member is properly classified as MH susceptible. (4) In patients with known NMD there is no indication for performing IVCT, since the results may even be misleading.
Mortier
W
W
Kinderklinik, Stadt Wuppertal.
Breucking
E
E
D000328:Adult; D002110:Caffeine; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000175:diagnosis*; D006221:Halothane; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008305:Malignant Hyperthermia; D012189:Retrospective Studies
D002110:Caffeine; D006221:Halothane
Diagnostik der Disposition zur malignen Hyperthermie. Teil 1: Bedutung des In vitro-Kontraktur-Tests.