{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:54:10Z","timestamp":1787997250428,"version":"build-2784847793"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Practical Research Project for Rare\/Intractable Diseases"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP19ek0109273"],"award-info":[{"award-number":["JP19ek0109273"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20ek0109468"],"award-info":[{"award-number":["JP20ek0109468"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Leigh syndrome is a neurodegenerative disorder caused by mitochondrial dysfunction with both phenotypic and genetic heterogeneity. Mitochondrial impairments are usually demonstrated by skeletal muscle biopsy. We report a case of Leigh syndrome diagnosed by endomyocardial biopsy (EMB), not by skeletal muscle biopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case summary<\/jats:title>\n                    <jats:p>At aged 7\u2009months, the patient had delayed motor development. He developed metabolic acidosis triggered by an infection with elevated lactate and pyruvate values in serum and cerebrospinal fluid when he was 1\u2009year old. T2-weighted imaging on magnetic resonance imaging of the brain revealed bilateral hyperintensity in midbrain and dorsal pons. Biopsied skeletal muscle did not show evidence of mitochondrial disease. Left ventricular hypertrophy, bilateral putamen hyperintensity in T2-weighted imaging and a lactate peak in the right basal ganglia in single voxel spectroscopy, and a convulsive seizure appeared at the age of 12, 15, and 16, respectively. When he was 17\u2009years old, biopsied myocardium showed cytoplasmic vacuolization and a marked proliferation of mitochondria within myofibrils pathologically. Respiratory chain enzyme activity of the biopsied myocardium showed decreased activity of complex I. Genetic testing revealed an m.14453 A&amp;gt;G mutation on the MT-ND6 gene. He was finally diagnosed with Leigh syndrome. Administration of oral 5-aminolevulinic acid reduced the frequency of seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>EMB led to the diagnosis of Leigh syndrome. Efforts to find and conduct the biopsy of affected organs are important to diagnose mitochondrial disease. EMB is a useful diagnostic method when there is a difficulty in diagnosing mitochondrial disease by skeletal muscle biopsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcr\/ytaa582","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T14:23:13Z","timestamp":1612794193000},"source":"Crossref","is-referenced-by-count":10,"title":["A case report of Leigh syndrome diagnosed by endomyocardial biopsy"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-6569","authenticated-orcid":false,"given":"Yuji","family":"Maruo","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan"},{"name":"Department of Pediatrics, Japanese Red Cross Kitami Hospital, North 6 East 2, Kitami 090-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3923-8636","authenticated-orcid":false,"given":"Kei","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Center for Medical Genetics, Chiba Children\u2019s Hospital, 579-1 Heta-cho, Midori-ku, Chiba 266-0007, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhito","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"2021020806462189100_ytaa582-B1","first-page":"221","article-title":"The genetics of Leigh syndrome and its implications for clinical practice and risk management","volume":"7","author":"Ruhoy","year":"2014","journal-title":"Appl Clin Genet"},{"key":"2021020806462189100_ytaa582-B2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/jnnp-2012-304426","article-title":"A guide to diagnosis and treatment of Leigh syndrome","volume":"85","author":"Baertling","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2021020806462189100_ytaa582-B3","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1212\/01.WNL.0000033795.17156.00","article-title":"Diagnostic criteria for respiratory chain disorders in adults and children","volume":"59","author":"Bernier","year":"2002","journal-title":"Neurology"},{"key":"2021020806462189100_ytaa582-B4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1053\/euhj.2000.2399","article-title":"New normal limits for the paediatric electrocardiogram","volume":"22","author":"Rijnbeek","year":"2001","journal-title":"Eur Heart J"},{"key":"2021020806462189100_ytaa582-B5","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.echo.2008.02.006","article-title":"Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study","volume":"21","author":"Pettersen","year":"2008","journal-title":"J Am Soc Echocardiogr"},{"key":"2021020806462189100_ytaa582-B6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/0002-9149(86)90771-X","article-title":"Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings","volume":"57","author":"Devereux","year":"1986","journal-title":"Am J Cardiol"},{"key":"2021020806462189100_ytaa582-B7","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1161\/CIRCULATIONAHA.107.741157","article-title":"A novel method of expressing left ventricular mass relative to body size in children","volume":"117","author":"Foster","year":"2008","journal-title":"Circulation"},{"key":"2021020806462189100_ytaa582-B8","doi-asserted-by":"crossref","DOI":"10.1136\/jclinpath-2020-206801","article-title":"Advanced pathological study for definite diagnosis of mitochondrial cardiomyopathy","author":"Takeda","year":"2020","journal-title":"J Clin Pathol"},{"key":"2021020806462189100_ytaa582-B9","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1212\/WNL.52.6.1255","article-title":"Respiratory chain complex I deficiency: an underdiagnosed energy generation disorder","volume":"52","author":"Kirby","year":"1999","journal-title":"Neurology"},{"key":"2021020806462189100_ytaa582-B10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00431-008-0753-7","article-title":"Intractable secretory diarrhea in a Japanese boy with mitochondrial respiratory chain complex I deficiency","volume":"168","author":"Murayama","year":"2009","journal-title":"Eur J Pediatr"},{"key":"2021020806462189100_ytaa582-B11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.mito.2012.01.001","article-title":"Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells","volume":"12","author":"Invernizzi","year":"2012","journal-title":"Mitochondrion"},{"key":"2021020806462189100_ytaa582-B12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem J"},{"key":"2021020806462189100_ytaa582-B13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s10545-017-0042-6","article-title":"Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients","volume":"40","author":"Ogawa","year":"2017","journal-title":"J Inherit Metab Dis"},{"key":"2021020806462189100_ytaa582-B14","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1515\/cclm-2020-0150","article-title":"A novel mitochondrial m.14430A&gt;G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome","volume":"58","author":"Du","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"2021020806462189100_ytaa582-B15","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/sj.ejhg.5200712","article-title":"An mtDNA mutation, 14453G\u2013&gt;A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome","volume":"9","author":"Ravn","year":"2001","journal-title":"Eur J Hum Genet"},{"key":"2021020806462189100_ytaa582-B16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00415-015-7884-3","article-title":"Mitochondrial disease: genetics and management","volume":"263","author":"Ng","year":"2016","journal-title":"J Neurol"},{"key":"2021020806462189100_ytaa582-B17","first-page":"428","article-title":"A new mitochondrial disease associated with mitochondrial DNA heteroplasmy","volume":"46","author":"Holt","year":"1990","journal-title":"Am J Hum Genet"},{"key":"2021020806462189100_ytaa582-B18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0140-6736(99)05225-3","article-title":"Mitochondrial respiratory chain disorders I: mitochondrial DNA defects","volume":"355","author":"Leonard","year":"2000","journal-title":"Lancet"},{"key":"2021020806462189100_ytaa582-B19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0140-6736(99)05226-5","article-title":"Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects","volume":"355","author":"Leonard","year":"2000","journal-title":"Lancet"},{"key":"2021020806462189100_ytaa582-B20","first-page":"53","article-title":"Mitochondrial cardiomyopathy","volume":"4","author":"Takeda","year":"2020","journal-title":"J Pediatr Cardiol Card Surg"},{"key":"2021020806462189100_ytaa582-B21","first-page":"385","article-title":"Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management","volume":"40","author":"Meyers","year":"2013","journal-title":"Tex Heart Inst J"},{"key":"2021020806462189100_ytaa582-B22","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3988\/jcn.2016.12.2.181","article-title":"Leigh syndrome in childhood: neurologic progression and functional outcome","volume":"12","author":"Lee","year":"2016","journal-title":"J Clin Neurol"},{"key":"2021020806462189100_ytaa582-B23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1750-1172-9-52","article-title":"A multicenter study on Leigh syndrome: disease course and predictors of survival","volume":"9","author":"Sofou","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"2021020806462189100_ytaa582-B24","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1093\/eurheartj\/ehs275","article-title":"Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management","volume":"33","author":"Bates","year":"2012","journal-title":"Eur Heart J"},{"key":"2021020806462189100_ytaa582-B25","doi-asserted-by":"crossref","first-page":"10549","DOI":"10.1038\/s41598-019-46772-x","article-title":"Effects of 5-aminolevulinic acid and sodium ferrous citrate on fibroblasts from individuals with mitochondrial diseases","volume":"9","author":"Shimura","year":"2019","journal-title":"Sci Rep"}],"container-title":["European Heart Journal - Case Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ehjcr\/article-pdf\/5\/2\/ytaa582\/36210921\/ytaa582.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ehjcr\/article-pdf\/5\/2\/ytaa582\/36210921\/ytaa582.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T14:23:31Z","timestamp":1612794211000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcr\/article\/doi\/10.1093\/ehjcr\/ytaa582\/6130191"}},"subtitle":[],"editor":[{"given":"Brian","family":"Halliday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Inga","family":"Voges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Luis Antonio","family":"Moreno-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Reshma","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Mariame","family":"Chakir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjcr\/ytaa582","relation":{},"ISSN":["2514-2119"],"issn-type":[{"value":"2514-2119","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,1]]},"published":{"date-parts":[[2021,2,1]]},"article-number":"ytaa582"}}