PT -期刊文章盟Caterina加隆AU -埃巴萨盟Karin Kleinsteuber AU -爱丽丝Donati AU -萨尔瓦多DiMauro盟渡Hirano TI -临床和分子遗传学的胸苷激酶缺2 (P5.067) DP - 2015年4月06 TA -神经病学PG - P5.067 VI - 84 IP - 14补充4099 - //www.ez-admanager.com/content/84/14_Supplement/P5.067.short 4100 - http://n.neurolo首页gy.org/content/84/14_Supplement/P5.067.full所以Neurology2015 4月06;84 AB -目的:描述四个新2胸苷激酶基因(TK2)患者的基因突变,并审查TK2缺乏症的临床和分子遗传学方面。背景:常染色体隐性(AR) TK2突变引起严重mtDNA枯竭和毁灭性的婴儿和儿童的神经肌肉疾病,以及mtDNA多个删除和进步的外部眼肌麻痹(PEO)的成年人。最近,与deoxypyrimidine mono磷酸盐分子搭桥治疗已经证明有效的改善Tk2缺乏在H126N兄弟小鼠模型。设计/方法:我们回顾了临床历史,分子遗传学和生化缺陷已报告65例,2001年至2014年在文学以及四个新患者TK2突变。结果:新四个病人,发病范围从小儿病人(1)儿童发病患者(2 - 4)在年轻患者发病最严重的临床过程。小说在TK2缺乏患者临床特征包括肌红蛋白尿症,多发性骨折和心律失常患者中观察到1和4。基于我们的新病人的病史和系统性的文献综述,我们确定了四个疾病报告:我)小儿encephalomyopathy发生在生命的第一年和快速进步的早逝;(二)童年SMA-like肌病进步移动多年的损失;iii)成人肌病与亚临床或轻度肌病发病和移动的逐渐丧失,呼吸衰竭,或在成年期; and iv) adult AR-PEO. Molecular genetics defects in muscle range from i) severe mtDNA depletion in the infantile/childhood onset forms, ii) coexisting mtDNA multiple depletion and mild mtDNA depletion in adult-onset myopathy, and iii) isolated mtDNA multiple deletions in AR-PEO. CONCLUSIONS: TK2 deficiency manifests a clinical and molecular genetic disease spectrum. Early and accurate diagnosis is important to initiate timely treatment with dCMP/dTMP, which may modify clinical history of this devastating disorder.Disclosure: Dr. Garone has nothing to disclose. Dr. Barca has nothing to disclose. Dr. Kleinsteuber has nothing to disclose. Dr. Donati has nothing to disclose. Dr. DiMauro has received personal compensation in an editorial capacity for MedLink Neurology. Dr. Hirano has received personal compensation in an editorial capacity for Medlink. Dr. Hirano has received research support from Santhera Pharmaceutical, Pfizer Inc., and Edison Pharmaceuticals.Wednesday, April 22 2015, 2:00 pm-6:30 pm