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Phenotypic patterns of MELAS/LS overlap syndrome associated with m.13513G>A mutation, and neuropathological findings
Zhaoxia Wang1, Xiao Kun Qi, Sheng Yao
1Department of Neurology, Peking University First Hospital, Beijing, China.
Abstract:
The 13513G>A mutation in the ND5 gene of mitochondrial DNA (mtDNA) is usually associated with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS), or Leigh syndrome (LS). In this study, we describe three young Chinese patients with MELAS/LS overlap syndrome who carried the m.13513G>A mutation. Clinical and MRI features were characteristic of both MELAS and LS. Interestingly, the clinical presentation of this overlap syndrome could be variable depending on the degree of relative contribution of MELAS and LS, that is, MELAS as the initial presenting syndrome, LS as the predominant syndrome, or both MELAS and LS appearing at the same time. The final brain MRI showed findings characteristic of both MELAS and LS, with asymmetrical lesions in the cortex and subcortical white matter of the occipital, temporal, and frontal lobes (MELAS), and bilateral and symmetrical lesions in the basal ganglia and brainstem (LS). Brain autopsy in one case revealed infarct-like lesions in the cerebral cortex, basal ganglia and brainstem, providing further insight into the distribution of the pathological lesions in MELAS/LS overlap syndrome. This is the first report of the brain pathological changes in a patient with m.13513G>A mutation. The spatial distribution of infarct-like lesions in the brain could explain the symptoms in MELAS/LS overlap syndrome.
Insights
The m.13513G>A mutation in mitochondrial DNA can cause MELAS/LS overlap syndrome. Brain autopsy in one case revealed infarct-like lesions, explaining the varied symptoms in this rare condition.
Area of Science:
- Genetics
- Neurology
- Pathology
Background:
- The m.13513G>A mutation in the ND5 gene of mitochondrial DNA (mtDNA) is linked to MELAS (mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes) and Leigh syndrome (LS).
- MELAS and LS are distinct mitochondrial disorders with overlapping clinical and neuroimaging features.
Observation:
- This study reports on three young Chinese patients presenting with MELAS/LS overlap syndrome, all carrying the m.13513G>A mutation.
- Patients exhibited clinical and MRI findings characteristic of both MELAS and LS.
- The clinical presentation varied, with MELAS or LS being the predominant or co-occurring syndrome.
Findings:
- Brain MRI revealed a combination of asymmetrical cortical/subcortical lesions (MELAS-like) and symmetrical basal ganglia/brainstem lesions (LS-like).
- Brain autopsy in one patient showed infarct-like lesions in the cerebral cortex, basal ganglia, and brainstem.
- This is the first report detailing brain pathological changes in a patient with the m.13513G>A mutation.
Implications:
- The spatial distribution of infarct-like lesions in the brain correlates with the diverse symptoms observed in MELAS/LS overlap syndrome.
- Understanding these pathological changes provides crucial insights into the pathogenesis of this specific mtDNA mutation.
- This study highlights the variability of MELAS/LS overlap syndrome and the importance of genetic testing for the m.13513G>A mutation.
