Screening Of The Novel RyR1Gene Mutation In A Patient With Malignant Hyperthermia Syndrome

Objective To study the definition of Malignant hyperthermia Syndrome，and itsclinical diagnosis and treatment and differential diagnosises；To study moleculargenetic mechanism of Malignant hyperthermia Syndrome by genetic screening.Materials and Methods1. Clinical characteristics：A38-year-old, healthy woman was admitted for thyroidtumor opreation with intravenous anesthesia. After operation, the patient had got highfever, muscle spasm. Myoglobinuria was detected and serum creatinase levelincreased significantly. One day late, acute renal failure appeared.2.Clinical intervention： Mythylprenisolone pulse therapy combined withhemodialysis were started after diagnosis.3. Muscular biopsy：At8weeks after the operation，gastrocnemius muscle biopsywas performed. The muscle specimens were examined by First affiliated Hospital ofSun Yat-sen Medical University. Specimens for light-microscopy were stained byHE、MGT、NADH-TR、ATPase、ORO and PAS.4. Kidney biopsy：Two times of renal biopsy were performed after1weeks and10weeks of surgery. The kidney tissue specimens were sent to Guangzhou Military AreaGeneral Hospital for light and electron microscopic study.5. Screening of RyR1：5ml peripheral blood was collected and frozen in-80℃.The DNA was extracted from white blood cells with phenol and106exons in RYR1was screened for mutation by Sangon biotech（shanghai）Corp. Ltd.Results1. Clinical Diagnosis：Malignant hyperthermia Syndrome2. Prognosis： The patients has been successfully saved by hemodialysis andmythelprenisolone, but unfortunately， kidney function has not fully recovered.Maintenance hemodialysis will be needed after dischargement. 3.Pathologic Diagnosis：The light microscope results showed severe rhabdomyolysis.TEM images of gastrocnemius muscle biopsy revealed that mitochondria increased inthe muscle fibes, especially huddled in the skeletal muscle sarcolemma. The first renalbiopsy showed acute tubular necrosis (ATN)，accompanied heavy impairment ofglomerulus and myoglobin thrombli in tubular. The second renal biopse revealed thatgeneralized changes of glomerulus of kidney and obstructive tubular necrosis，accompanied extensive interstitial fibrosis.4. Genetic Diagnosis：Genetic results showed that seven coding-region SNPs havebeen found among106exons in RYR1, including p.ala359ala，p. ser556ser，p.pro762pro，p. thr982thr，p. ile1152ile，p. ala2428ala，p. pro2528pro.5. Clinical Differential Diagnosis：From this study, we suspected that the paitientshould have some form of nervomuscular diseases, including mitochondrial myopathy,myoadenylate deaminase deficiency, central core disesase and Carnitinepalmitoyltransferase II deficiency.Conclusion1. Many congenital birth defects in muscle may induce malignant hyperthermiasyndrome. For example， some reports suggested that neuromuscular diseases,including mitochondrial myopathy, myoadenylate deaminase deficiency and carnitinepalmitoyltransferase II deficiency were the possible genetic susceptible factor forMHS.2. Acute tubular necrosis (ATN) caused by rhabdomyolysis may possiblely progressto Chronic Renal Failure. This may be part because the ATN accompanied by severeglomerulus impairment and disturbance of energy metabolism in kidneymitochondria.3. Seven coding-region SNPs in RyR1have been screened and one of which is anovel mutation to date. And these mutations can cause anormal expression of aquaporins through mispelling control, stability of mRNA, efficiency of proteintranslation and structural change of protein.