Genomic Screening for Malignant Hyperthermia Susceptibility.
Genomic Screening for Malignant Hyperthermia Susceptibility.
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DOI：
10.1097/aln.0000000000003547
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发表时间：
2020-12-01
期刊：
影响因子：
8.8
通讯作者：
Weber J
中科院分区：
文献类型：
--
作者：
Biesecker LG;Dirksen RT;Girard T;Hopkins PM;Riazi S;Rosenberg H;Stowell K;Weber J
恶性高热症（MH）在60年前被描述，我们对该综合征的临床和病理生理特征的理解不断进步。MH可归因于基因决定的对强效吸入麻醉剂（如异氟醚）或琥珀酰胆碱引发的骨骼肌细胞钙通量异常的易感性。自1979年丹曲林钠被批准以来，恶性高热的死亡率大幅下降，但仍保持在4-10%。恶性高热反应的确切发生率尚不清楚，但可能高达25000个麻醉药中有一个。三种基因的变异导致对这种疾病的易感性。RYR1基因最为常见，其次是CACNA1S和STAC3。虽然咖啡因-氟烷挛缩试验和体外挛缩试验被认为是诊断恶性高热易感性的金标准，但在基因检测方面已经取得了重要进展。由于这些进展，该领域考虑使用基因组检测筛查恶性高热易感性的效用和实用性是及时的。在这里，我们提出了一个简单而大胆的问题；怎样才能终结恶性高热造成的死亡？我们回顾了最近的进展，并提出了实现这一大胆目标的科学和临床途径，以引发该领域的讨论。
Malignant Hyperthermia(MH) was described 60 years ago and our understanding of the clinical and pathophysiologic features of this syndrome continue to advance. MH is attributed to a genetically determined susceptibility to an abnormal skeletal muscle cell calcium flux triggered by potent inhalation anesthetics (e.g., isoflurane) or succinylcholine. Since dantrolene sodium was approved in 1979 the mortality from malignant hyperthermia dropped substantially, but remains 4-10%. The exact incidence of malignant hyperthermia reactions is unknown but may be as high as one in 25,000 anesthetics. Variants in three genes cause the susceptibility to this disorder. The RYR1 gene is most common followed by CACNA1S and STAC3. While the caffeine-halothane contracture test and the in vitro contracture test are considered the gold standards for diagnosis of susceptibility to malignant hyperthermia, there have been important advances in genetic testing. Due to these advances, it is timely for the field to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here we pose a simple, but bold question; what would it take to end deaths from malignant hyperthermia? We review recent advances and propose a scientific and clinical pathway toward this audacious goal to provoke discussion in the field.