线粒体3-羟基3-甲基戊二酰辅酶A合成酶缺乏症（HMCSD）是由于HMGCS2基因变异导致的罕见酮体生成障碍疾病。该研究报道1例该病。患者，女，8个月，因腹泻1周，发热、抽搐1天入院，病程中出现抽搐以及酸中毒、低血糖、肝功能损害、心肌损伤、凝血功能异常等表现。基因检测发现患者HMGCS2基因存在新发c.1502G > A（p.R501Q）纯合突变，生物信息学软件分析提示有害；尿有机酸分析提示4-羟基-6-甲基-2-吡喃酮明显增高，与基因检测结果吻合。患者最后确诊为HMCSD。
Abstract
Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency (HMCSD) is caused by HMGCS2 gene mutation. This paper reports the clinical and genetic features of an infant with this disease. The 8-month-old female infant was admitted to the hospital with diarrhea for 1 week and fever and convulsion for 1 day. The child presented with seizures, acidosis, hypoglycemia, abnormal liver function, myocardial injury and coagulation dysfunction. The new homozygous mutation c.1502G > A(p.R501Q) in the HMGCS2 gene was found in the infant by genetic testing. The mutant gene was found to be harmful by bioinformatics software analysis. Urine organic acid analysis indicated that 4-hydroxy-6-methyl-2-pyranone was significantly increased, which was consistent with the results of genetic testing. The infant was definitely diagnosed with HMCSD.
关键词
线粒体3-羟基3-甲基戊二酰辅酶A合成酶缺乏症 /
尿代谢谱 /
HMGCS2基因 /
婴儿
Key words
Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency /
Urine metabolic spectrum /
HMGCS2 gene /
Infant
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参考文献
[1] Wolf NI, Rahman S, Clayton PT, et al. Mitochondrial HMGCoA synthase deficiency:identification of two further patients carrying two novel mutations[J]. Eur J Pediatr, 2003, 162(4):279-280.
[2] Aledo R, Zschocke J, Pié J, et al. Genetic basis of mitochondrial HMG-CoA synthase deficiency[J]. Hum Genet, 2001, 109(1):19-23.
[3] Ramos M, Menao S, Arnedo M, et al. New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations[J]. Eur J Med Genet, 2013, 56(8):411-415.
[4] Cotter DG, Ercal B, Huang X, et al. Ketogenesis prevents dietinduced fatty liver injury and hyperglycemia[J]. J Clin Invest, 2014, 124(12):5175-5190.
[5] Rescigno T, Capasso A, Tecce MF, et al. Involvement of nutrients and nutritional mediators in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression[J]. J Cell Physiol, 2018, 233(4):3306-3314.
[6] Puisac B, Ramos M, Arnedo M, et al. Characterization of splice variants of the genes encoding human mitochondrial HMGCoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway[J]. Mol Biol Rep, 2012, 39(4):4777-4785.
[7] Shafqat N, Turnbull A, Zschocke J, et al. Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design[J]. J Mol Biol, 2010, 398(4):497-506.
[8] Fukao T, Mitchell G, Sass JO, et al. Ketone body metabolism and its defects[J]. J Inherit Metab Dis, 2014, 37(4):541-551.
[9] Thompson GN, Hsu BY, Pitt JJ, et al. Fasting hypoketotic coma in a childwith deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase[J]. N Engl J Med, 1997, 337:1203-1207.
[10] Bouchard L, Robert MF, Vinarov D, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:clinical course and description of causal mutations in two patients[J]. Pediatr Res, 2001, 49(3):326-331.
[11] Puisac B, Marcos-Alcalde I, Hernández-Marcos M, et al. Human mitochondrial HMG-CoA synthase deficiency:role of enzyme dimerization surface and characterization of three new patients[J]. Int J Mol Sci, 2018, 19(4). pii:E1010. doi:10.3390/ijms19041010.
[12] Pitt JJ, Peters H, Boneh A, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:urinary organic acid profiles and expanded spectrum of mutations[J]. J Inherit Metab Dis, 2015, 38(3):459-466.
[13] Conboy E, Vairo F, Schultz M, et al. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency:Unique presenting laboratory values and a review of biochemical and clinical features[J]. JIMD Rep, 2018, 40:63-69.
[14] Aledo R, Mir C, Dalton RN, et al. Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency[J]. J Inherit Metab Dis, 2006, 29(1):207-211.
基金
四川省科技厅重点研发项目（2018SZ0123）。
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