Investigation of a family following fulminant malignant hyperthermia.
Malignant hyperthermia (MH) is a pharmacogenetic neuromuscular disorder triggered by inhalational anesthetics or succinylcholine. We studied in detail 24 relatives of a patient who died after experiencing MH. All steps of the screening procedure follow developments in testing for the diagnosis of MH susceptibility from 1984 until 2002.


METHODS
: The screening procedure contained a general assessment and a clinical examination; creatine kinase (CK) measurement; genomic DNA isolation for linkage analysis and mutation screening; muscle samples were tested according to the in vitro contracture test protocol (IVCT) and examined histologically; and cultured skeletal muscle cells were used to examine the effect of halothane on the intracellular calcium concentration.


RESULTS
: No correlation was found between IVCT results, serum CK, or abnormal findings after histologic examination, although CK elevation and the observation of cores seemed indicative for MH susceptibility in this family. Linkage analysis implicated RYR1 on chromosome 19q13.1 as the disease susceptibility locus in the family. The calcium response was found to be significantly different.


CONCLUSIONS
: Following 3 decades of screening for MH, the gold standard for diagnosis remains the IVCT for detection of susceptibility to MH.
Snoeck
Marc
M
From the Department of *Anaesthesia, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands; the Departments of daggerPaediatrics, section signNeuromorphology, and paragraph signNeurology, University of Nijmegen, The Netherlands; the double daggerSchool of Biology, University of Leeds, U.K.; and the parallelMH Investigation Unit, St. James' University Hospital Leeds, U.K.
Sengers
Rob
R
Iles
David
D
Ter Laak
Henk
H
Robinson
Rachel
R
Padberg
George
G