Sun28November0333PM 27

A 24-year-old woman has been referred to a malignant hyperthermia (MH) investigation unit following a general anaesthetic.

Which one of the following options is the most appropriate investigation that will establish malignant hyperthermia susceptibility?

(Please select 1 option)

In vitro muscle contraction test using 4-chloro-m-cresol

In vitro muscle contraction test using caffeine This is the correct answer

Serum creatine kinase (CK)

Chromosomal analysis Incorrect answer selected

In vitro muscle contraction test using ryanodine

Explanation

Malignant hyperthermia is a genetically inherited condition of skeletal muscle with an autosomal dominant mode of inheritance.

The in vitro muscle contracture test (IVCT) is the standard test to establish an individual's risk of susceptibility to malignant hyperthermia. A muscle biopsy is taken from the patient's vastus medialis or lateralis under regional anaesthesia (not local infiltration or general anaesthesia). Muscle fibres are subjected to exposure to increasing concentrations of halothane and caffeine and the force of muscle contraction measured when stretched (dynamic test).

The ryanodine contracture test (RCT) using the plant alkaloid ryanodine as the triggering agent has been proposed to reduce equivocal results of the in vitro caffeine-halothane-contracture test (IVCT), which is the accepted and standardised procedure to diagnose MH. However, the response of skeletal muscle of non-MH affected patients (controls) to ryanodine has not yet been characterised.

Although in vitro contracture testing for malignant hyperthermia diagnosis is well standardised, with a relatively high sensitivity and specificity, false test results cannot be excluded and may be associated with serious disabilities for the concerned individuals. 4-chloro-m-cresol (a ryanodine receptor-specific agonist) has been evaluated as a new test substance for the in vitro contracture testing. Its use improves the accuracy of in vitro diagnosis of malignant hyperthermia susceptibility.

Genetic analyses mapped the malignant hyperthermia (MH) susceptibility trait to the ryanodine receptor locus (RYR1) on chromosome 19q12-13.2. This gene encodes the skeletal muscle sarcoplasmic reticulum calcium release channel, a key protein involved in the process of excitation-contraction coupling. To date, over 30 different mutations have been detected in the gene and 15 of these have been functionally characterised using in vitro cellular assays and are considered causative of MH. A patient and relatives would normally be genetically investigated if IVCTs proved positive.

Raised plasma creatine kinase (CK) during an acute episode of MH may reflect muscle damage but is not specific to this condition.

Answer Statistics

1

7%

2

55%

3

4%

4

13%

5

23%

Times answered: 270