Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background
Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background
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DOI：
10.1016/j.ijcard.2019.01.017
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发表时间：
2019-03-15
影响因子：
3.5
通讯作者：
Okazaki, Yasushi
中科院分区：
文献类型：
--
作者：
Imai-Okazaki, Atsuko;Kishita, Yoshihito;Okazaki, Yasushi
背景：心肌病是线粒体病患儿预后不良的一个指标。然而，线粒体病患儿心肌病的遗传背景与预后之间的关系尚未完全阐明。方法和结果：在2004年至2018年期间进行基因诊断的137名线粒体病患儿中，有29名患有线粒体心肌病（21%）。中位随访35个月后，心肌病患者的总生存率显著低于无心肌病患者（p <0.001），Kaplan-Meier估计的10年总生存率分别为18%和67%。在死亡的21名心肌病患者中，有两名在出生后一个月内死亡（1名患者为COQ 4，1名患者为COXIO），10名患者在一年内死亡（三名患者中的BOLA 3，两名患者中的QRSLI，两名患者中的大染色体缺失，一名患者中的MT-ATP 6/8，一名患者中的MT-111，和一名患者中的TAZ基因），9例患者在一年后死亡（3例患者中的MT-ND 5，3例患者中的MT-111，1例患者中的ACAD 9，1例患者中的KARS，以及1例患者中的MT-TV）。在三名心肌组织可用的线粒体DNA突变患者中，观察到m8528 T-C在心肌组织中的高异质性率（90%，2月龄时死亡）和m. 3243 A-G（90%和80%分别在12岁和13岁时死亡）。在患有线粒体疾病的儿童中，心肌病是常见的（21%），并与死亡率增加有关。基因分析加上详细的表型可能有助于预后。(C)2019由Elsevier B. V.出版
Background: Cardiomyopathy is a reported indicator of poor prognosis in children with mitochondria' disease. However, the association between prognosis and the genetic background of cardiomyopathy in children with mitochondria' disease has yet to be fully elucidated.Methods and results: Of 137 children with mitochondria' disease whose genetic diagnosis was made between 2004 and 2018,29 had mitochondrial cardiomyopathy (21%). After a median follow-up of 35 months, the overall survival rate was significantly lower in patients with cardiomyopathy than in those without (p < 0001), Ten-year Kaplan-Meier estimates of overall survival were 18 and 67%, respectively. Among the 21 cardiomyopathy patients who died, two died within one month of birth (COQ4 in one patient, and COXIO in one patient), ten died within one year (BOLA3 in three patients, QRSLI in two patients, large chromosomal deletions in two patients, MT-ATP6/8 in one patient, MT-111 in one patient, and TAZ gene in one patient), and nine died after one year (MT-ND5 in three patients, MT-111 in three patients, ACAD9 in one patient, KARS in one patient, and MT-TV in one patient). In the three patients with mitochondrial DNA mutations whose cardiac tissues were available, high heteroplasmy rates in the cardiac tissue were observed for m8528T---C (90%, died at 2 months of age) and m.3243A---G (90 and 80%, died at 12 and 13 years of age, respectively).Conclusions: In children with mitochondrial disease, cardiomyopathy was common (21%) and was associated with increase(' mortality. Genetic analysis coupled with detailed phenotyping could be useful for prognosis. (C) 2019 Published by Elsevier B.V.