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MELAS syndrome patients typically present in the first two decades of life with a broad, multi\u2010systemic phenotype that predominantly features neurological manifestations\u2013\u2013stroke\u2010like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2009years and seizures are the most prevalent manifestation of stroke\u2010like episodes. Heteroplasmy is higher in a tissue other than blood in most cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A&gt;G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1955","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T05:23:53Z","timestamp":1651037033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-3688","authenticated-orcid":false,"given":"Lydia M.","family":"Seed","sequence":"first","affiliation":[{"name":"School of Clinical Medicine University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-8448","authenticated-orcid":false,"given":"Andrew","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience University of Cambridge  Cambridge UK"},{"name":"Department of Histopathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Krishnakumar","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurosciences Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poe","family":"Phyu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroradiology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-170X","authenticated-orcid":false,"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-567X","authenticated-orcid":false,"given":"Pooja Devi","family":"Harijan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurosciences Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2017.01.029"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.4.955"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A6325"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.01.157"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2011.06.004"},{"key":"e_1_2_12_7_1","article-title":"Contribution of nuclear and mitochondrial gene mutations in mitochondrial encephalopathy, lactic acidosis, and stroke\u2010like episodes (MELAS) syndrome","volume":"1","author":"Chakrabarty S.","year":"2021","journal-title":"Journal of Neurology"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.02.015"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261929.92478.3e"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.06.004"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812445787"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.66.1.8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.43.1126"},{"issue":"2","key":"e_1_2_12_14_1","first-page":"1","article-title":"Mitochondrial diseases","volume":"21","author":"Gorman G. 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