Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with m.3243A>G Mutation in Mitochondrial DNA.
Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with m.3243A>G Mutation in Mitochondrial DNA.
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100例中国线粒体DNA m.3243A>G突变患儿的临床和分子特征
DOI：
10.4103/0366-6999.187845
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发表时间：
2016-08-20
影响因子：
6.1
通讯作者：
Qi Y
中科院分区：
文献类型：
--
作者：
Xia CY;Liu Y;Liu H;Zhang YC;Ma YN;Qi Y
背景：线粒体疾病是一组多系统受累的能量代谢紊乱。多变的临床特征是儿科诊断的主要挑战。我们总结了中国儿童m.3243A>G突变的临床谱，明确常见的临床表现，研究突变异质性程度与疾病严重程度的相关性。方法：回顾性分析2007 - 2013年100例m.3243A>G突变的症状性线粒体疾病患儿的临床资料。采用聚合酶链反应-限制性片段长度多态性方法检测m.3243A>G突变率。分析m.3243A>G突变率与年龄的相关性。采用卡方检验分析突变率低、中、高水平患者临床症状频率的差异。结果：66例（66%）患者的诊断延迟平均2年。最常见的症状是癫痫发作（76%）、身材矮小（73%）、血浆乳酸升高（70%）、异常磁共振成像/计算机断层扫描（MRI/CT）变化（68%）、呕吐（55%）、视力下降（52%）、头痛（50%）和肌无力（48%）。突变率与发病年龄呈负相关（r =-0.470，P < 0.001）。肌病在高突变率的患者中更常见。然而，具有低或中等水平的m.3243A>G突变比率的患者比具有高水平突变比率的患者更容易遭受听力损失、视力下降和胃肠道紊乱。结论：我们的研究表明，一半的m.3243A>G突变的中国儿童患者表现为癫痫发作、身材矮小、异常MRI/CT改变、血浆乳酸升高、呕吐和头痛。有这些复发症状的儿童患者应考虑筛查m.3243A>G突变。临床表现和实验室异常应密切监测患者与此点突变。
Background:Mitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease. Methods:Clinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test. Results:Sixty-six patients (66%) had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures (76%), short stature (73%), elevated plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography (MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%), and muscle weakness (48%). The mutation ratio was correlated negatively with onset age (r = −0.470, P < 0.001). Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio. Conclusions:Our study showed that half of Chinese pediatric patients with m.3243A>G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A>G mutation. Clinical manifestations and laboratory abnormalities should be carefully monitored in patients with this point mutation.