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Wolff-Parkinson-White syndrome in Patients With MELAS
Douglas M Sproule1, Petra Kaufmann, Kristen Engelstad
1Division of Pediatric Neurology, Department of Neurology, Columbia University, New York, NY, USA.
Background:
Tissues with high energy demands, such as the heart, are susceptible to the effects of mitochondrial DNA point mutations.
Objective:
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.
Design:
Survey.
Setting:
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.
Interventions:
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.
Results:
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.
Conclusions:
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.
Insights
Wolff-Parkinson-White (WPW) syndrome is more common in patients with MELAS syndrome and the A3243G mutation than in the general population. Early screening for WPW syndrome is recommended in patients with MELAS syndrome.
Area of Science:
- Cardiology and Neurology
- Mitochondrial Genetics
Background:
- Mitochondrial DNA point mutations affect tissues with high energy demands, like the heart.
- MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome is linked to the A3243G mutation.
Purpose of the Study:
- To determine the frequency of Wolff-Parkinson-White (WPW) syndrome in patients with MELAS syndrome and the A3243G mutation.
- To assess if WPW syndrome presentation precedes MELAS syndrome symptoms.
Main Methods:
- A survey of 30 patients with MELAS syndrome and the A3243G mutation.
- Review of medical histories and electrocardiograms.
- Analysis of mitochondrial mutation abundance and total mutation burden from various tissue samples.
Main Results:
- 13% (4 out of 30) of patients had WPW syndrome.
- In two cases, WPW syndrome appeared 15 and 21 years before MELAS syndrome.
- Similar tissue burden of mutant mitochondria was observed in patients with and without WPW syndrome.
Conclusions:
- WPW syndrome is more prevalent in MELAS syndrome patients with the A3243G mutation than in the general population.
- WPW syndrome may manifest earlier than neurological symptoms in these patients.
- Screening for the A3243G mutation is advised for patients with WPW and MELAS-like neurological symptoms; cardiac monitoring is recommended for MELAS patients.
