• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Inborn Errors of Metabolism & Screening >Isolated and Combined Remethylation Disorders Biochemical and Genetic Diagnosis and Pathophysiology
【24h】

Isolated and Combined Remethylation Disorders Biochemical and Genetic Diagnosis and Pathophysiology

机译：分离和合并的重甲基化疾病生化和遗传诊断与病理生理学

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Genetic defects affecting the remethylation pathway cause hyperhomocysteinemia. Isolated remethylation defects are caused by mutations of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) , methionine synthase reductase (MTRR) , methionine synthase (MTR) , and MMADHC genes, and combined remethylation defects are the result of mutations in genes involved in the synthesis of either methylcobalamin or adenosylcobalamin, that is, the active cofactors of MTRR and methylmalonyl-CoA mutase. Diagnosis is based on the biochemical analysis of amino acids, homocysteine, propionylcarnitine, methylmalonic acid, S-adenosylmethionine, and 5-methylentetrahydrofolate in physiological fluids. Gene-by-gene Sanger sequencing has long been the gold standard genetic analysis for confirming the disorder and identifying the gene involved, but massive parallel sequencing is now being used to examine all those potentially involved in one go. Early treatment to rescue metabolic homeostasis is based on the following of an appropriate diet, betaine administration, and, in some cases, oral or intramuscular administration of vitamin B 12 or folate. Elevated ROS levels, apoptosis, endoplasmic reticulum (ER) stress, the activation of autophagy, and alterations in Ca 2+ homeostasis may all contribute toward the pathogenesis of the disease. Pharmacological agents to restore the function of the ER and mitochondria and/or to reduce oxidative stress-induced apoptosis might provide novel ways of treating patients with remethylation disorders.
机译：影响再甲基化途径的遗传缺陷导致高同型半胱氨酸血症。单独的再甲基化缺陷是由5、10-亚甲基四氢叶酸还原酶（MTHFR），蛋氨酸合酶还原酶（MTRR），蛋氨酸合酶（MTR）和MMADHC基因的突变引起的，而合并的再甲基化缺陷是与该基因有关的基因突变的结果。合成甲基钴胺素或腺苷钴胺素，即MTRR和甲基丙二酰-CoA突变酶的活性辅因子。诊断基于生理液中氨基酸，高半胱氨酸，丙酰肉碱，甲基丙二酸，S-腺苷甲硫氨酸和5-甲基四氢叶酸的生化分析。逐个基因进行Sanger测序长期以来一直是确认该疾病和鉴定涉及基因的金标准遗传分析，但是现在正在使用大规模并行测序来一次性检查所有可能涉及的基因。抢救新陈代谢稳态的早期治疗基于适当饮食，甜菜碱的使用，以及在某些情况下口服或肌肉内施用维生素B 12或叶酸的治疗。 ROS水平升高，细胞凋亡，内质网（ER）应激，自噬激活和Ca 2+稳态改变均可能与疾病的发病机理有关。恢复ER和线粒体功能和/或减少氧化应激诱导的细胞凋亡的药理剂可能为治疗再甲基化疾病患者提供新的方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号