Denborough M
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra ACT.
Lancet. 1998 Oct 3;352(9134):1131-6. doi: 10.1016/S0140-6736(98)03078-5.
A specific inherited muscle membrane disorder predisposes to a variety of clinical problems. The most common is malignant hyperthermia (MH), a dangerous hypermetabolic state after anaesthesia with suxamethonium and/or volatile halogenated anaesthetic agents. MH may also be triggered in susceptible individuals by severe exercise in hot conditions, infections, neuroleptic drugs, and overheating in infants. Inbred pigs have provided a helpful model, and experiments on these animals and in MH-susceptible patients have shown that the essential biochemical abnormality is an increase in calcium ions in the muscle cells. This knowledge has led to a specific muscle test to identify susceptibility to MH and to a specific treatment, dantrolene; and as a result the case-fatality rate in MH has fallen from 70% in the 1970s to 5% today. In pigs susceptibility to MH is caused by a single mutation in the ryanodine receptor (RYR) in skeletal muscle. In man the genetics is more complex and three clinical myopathies that predispose to MH have been defined. By far the most common is inherited as a mendelian dominant characteristic and at present mutations in the human RYR account for no more than 20% of susceptible families.
一种特定的遗传性肌膜疾病易引发多种临床问题。最常见的是恶性高热（MH），这是一种在使用琥珀胆碱和/或挥发性卤化麻醉剂麻醉后出现的危险的高代谢状态。在易感个体中，高温环境下的剧烈运动、感染、抗精神病药物以及婴儿过热也可能引发恶性高热。近亲繁殖的猪提供了一个有用的模型，对这些动物以及恶性高热易感患者进行的实验表明，基本的生化异常是肌肉细胞中钙离子增加。这一认识催生了一项用于识别恶性高热易感性的特定肌肉测试以及一种特定的治疗方法——丹曲林；结果，恶性高热的病死率已从20世纪70年代的70%降至如今的5%。在猪中，对恶性高热的易感性是由骨骼肌中兰尼碱受体（RYR）的单一突变引起的。在人类中，遗传学情况更为复杂，目前已确定了三种易引发恶性高热的临床肌病。迄今为止最常见的是作为孟德尔显性特征遗传，目前人类兰尼碱受体的突变在易感家族中所占比例不超过20%。
