Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the most common mitochondrial disorders. Cardiovascular involvement has been reported in up to 30% of MELAS patients with varying clinical presentations from non-specific cardiogenic abnormalities to conduction abnormalities, cardiomyopathies, heart failure, fatal arrhythmias, and cardiac death. Although conduction defects are a known complication, the frequency of Wolff–Parkinson–White (WPW) syndrome among MELAS patients and patients carrying mutations associated with MELAS is uncertain, and their association with cardiomyopathy and treatment outcomes have rarely been reported. A retrospective chart review of fifty patients carrying m.3243A > G mutations was conducted at the Center for the Treatment of Pediatric Neurodegenerative Disease at UT Health Science Center Houston. Medical histories, electrocardiograms, echocardiograms, and electrophysiology studies from January 2007 to December 2022 were reviewed and DNA samples from buccal epithelial cells, blood, and hair were analyzed to determine the mitochondrial mutation and total mutation burden. Forty-three patients with m.3243A > G mutations were included in the analysis. Six of twenty-two patients with MELAS (30%), and two of twenty-one patients without MELAS (10%) had electrocardiographic findings consistent with WPW. Other conduction abnormalities were noted in eleven of twenty-two patients with MELAS (50%) and six out of twenty-one patients without MELAS (29%). Four patients (9%) required electrophysiology studies with ablation, one for inappropriate sinus tachycardia resistant to medical management, and three with WPW syndrome all of whom required repeat ablations. Conduction abnormalities were noted to have positive correlation with higher heteroplasmy levels (mean 37% vs 54%, 95% CI for mean difference = (− 32.5, − 2.82), p-value = 0.021). Six patients with MELAS (30%) had cardiomyopathy of varying severity which were all associated with conduction abnormalities, including two patients with WPW syndrome (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">${\chi }^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msup> <mrow> <mi>χ</mi> </mrow> <mn>2</mn> </msup> </math></EquationSource> </InlineEquation> with continuity correction p-value = 0.014). The prevalence of WPW in patients with MELAS syndrome secondary to the m.3243A > G variant appears much higher than in the normal population and may require multiple electrophysiology studies ablations to treat. Routine cardiology screening is recommended for early detection.

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Patients with m.3243A > G have High Prevalence of Wolff–Parkinson–White Syndrome

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发表日期：

2025年8月12日

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J. Y. Liu,
M. K. Koenig,
K. Riggs-Harpur,
M. T. Numan

摘要

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the most common mitochondrial disorders. Cardiovascular involvement has been reported in up to 30% of MELAS patients with varying clinical presentations from non-specific cardiogenic abnormalities to conduction abnormalities, cardiomyopathies, heart failure, fatal arrhythmias, and cardiac death. Although conduction defects are a known complication, the frequency of Wolff–Parkinson–White (WPW) syndrome among MELAS patients and patients carrying mutations associated with MELAS is uncertain, and their association with cardiomyopathy and treatment outcomes have rarely been reported. A retrospective chart review of fifty patients carrying m.3243A > G mutations was conducted at the Center for the Treatment of Pediatric Neurodegenerative Disease at UT Health Science Center Houston. Medical histories, electrocardiograms, echocardiograms, and electrophysiology studies from January 2007 to December 2022 were reviewed and DNA samples from buccal epithelial cells, blood, and hair were analyzed to determine the mitochondrial mutation and total mutation burden. Forty-three patients with m.3243A > G mutations were included in the analysis. Six of twenty-two patients with MELAS (30%), and two of twenty-one patients without MELAS (10%) had electrocardiographic findings consistent with WPW. Other conduction abnormalities were noted in eleven of twenty-two patients with MELAS (50%) and six out of twenty-one patients without MELAS (29%). Four patients (9%) required electrophysiology studies with ablation, one for inappropriate sinus tachycardia resistant to medical management, and three with WPW syndrome all of whom required repeat ablations. Conduction abnormalities were noted to have positive correlation with higher heteroplasmy levels (mean 37% vs 54%, 95% CI for mean difference = (− 32.5, − 2.82), p-value = 0.021). Six patients with MELAS (30%) had cardiomyopathy of varying severity which were all associated with conduction abnormalities, including two patients with WPW syndrome ( ${\chi }^{2}$ $χ^{2}$ with continuity correction p-value = 0.014). The prevalence of WPW in patients with MELAS syndrome secondary to the m.3243A > G variant appears much higher than in the normal population and may require multiple electrophysiology studies ablations to treat. Routine cardiology screening is recommended for early detection.