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Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature.

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Krishnakumar, Deepa 
Phyu, Poe 


BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi-systemic phenotype that predominantly features neurological manifestations--stroke-like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses. METHODS: A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed. RESULTS: Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke-like episodes. Heteroplasmy is higher in a tissue other than blood in most cases. CONCLUSION: The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.


Funder: Addenbrooke’s Charitable Trust, Cambridge University Hospitals; Id:

Funder: European Research Council; Id:

Funder: Evelyn Trust; Id:

Funder: Medical Research Council; Id:

Funder: Newton Fund; Id:

Funder: the Lily Foundation

Funder: The Stoneygate Trust

Funder: Wellcome Trust; Id:


MELAS syndrome, encephalopathy, genetics, lactic acidosis, m.3243A>G, mitochondrial disease, paediatric neurology, stroke-like episodes, Acidosis, Lactic, Child, Humans, MELAS Syndrome, Retrospective Studies, Seizures, Stroke

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Mol Genet Genomic Med

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MRC (MR/V009346/1)
Wellcome Trust (109915_A_15_Z)