Sproule Douglas M, Kaufmann Petra, Engelstad Kristen, Starc Thomas J, Hordof Allan J, De Vivo Darryl C
Division of Pediatric Neurology, Department of Neurology, Columbia University, New York, NY, USA.
Arch Neurol. 2007 Nov;64(11):1625-7. doi: 10.1001/archneur.64.11.1625.
Tissues with high energy demands, such as the heart, are susceptible to the effects of mitochondrial DNA point mutations.
To investigate the frequency of Wolff-Parkinson-White (WPW) syndrome among a phenotypically and genotypically homogeneous cohort of patients with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) and the A3243G mutation most commonly associated with MELAS syndrome.
Survey.
The Pediatric Neuromuscular Disease Center at Columbia University. Patients Thirty patients with the A3243G mutation and MELAS syndrome enrolled in a clinical trial to assess the effect of dichloroacetate on neurologic symptoms.
Medical histories and electrocardiograms were reviewed and DNA samples from fibroblasts, urine and cheek epithelial cells, leukocytes, and hair were analyzed to determine mitochondrial mutation abundance and estimate total mutation burden.
Four of 30 patients (13%) had a clinical history of, or electrocardiographic findings consistent with, WPW syndrome. In 2 patients, WPW syndrome preceded MELAS syndrome by 15 and 21 years. The tissue burden of mutant mitochondria was similar in patients with (49.4%) and without (39.1%) WPW syndrome.
The prevalence of WPW syndrome among patients with MELAS syndrome and the A3243G mutation appears much higher than in the normal population and may become manifest earlier than neurologic symptoms. Patients with WPW syndrome and neurologic abnormalities consistent with MELAS syndrome, such as seizures, deafness, short stature, and stroke, should be screened for the A3243G mutation. Moreover, patients with MELAS syndrome should be monitored for cardiac anomalies including cardiomyopathy and WPW syndrome.
心脏等能量需求高的组织易受线粒体DNA点突变的影响。
在表型和基因型均一的伴有MELAS（线粒体脑肌病伴乳酸血症和卒中样发作）及最常与MELAS综合征相关的A3243G突变的患者队列中，研究预激综合征（WPW）的发生率。
调查。
哥伦比亚大学儿科神经肌肉疾病中心。患者30例携带A3243G突变和MELAS综合征的患者参加了一项评估二氯乙酸对神经症状影响的临床试验。
回顾病史和心电图，并分析来自成纤维细胞、尿液、颊上皮细胞、白细胞和毛发的DNA样本，以确定线粒体突变丰度并估计总突变负荷。
30例患者中有4例（13%）有WPW综合征的临床病史或心电图表现与之相符。在2例患者中，WPW综合征比MELAS综合征早出现15年和21年。有WPW综合征（49.4%）和无WPW综合征（39.1%）患者的突变线粒体组织负荷相似。
伴有MELAS综合征和A3243G突变的患者中WPW综合征的患病率似乎远高于正常人群，且可能比神经症状出现得更早。对于有WPW综合征且有与MELAS综合征相符的神经异常（如癫痫、耳聋、身材矮小和卒中）的患者，应筛查A3243G突变。此外，对于MELAS综合征患者，应监测包括心肌病和WPW综合征在内的心脏异常情况。
