{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:32:43Z","timestamp":1786980763858,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T00:00:00Z","timestamp":1199664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Although linked with cardiac dysfunction, the association of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke\u2010like episodes) and pulmonary artery hypertension (PAH) has not been previously described. PAH and right ventricular heart failure were identified by echocardiography in a 3\u2010year\u2010old boy with a history of hypotonia, microcephaly and developmental delay. He initially presented with a 10\u2010day history of dyspnoea, dependent oedema and reduced oral intake. Lactic acidosis was noted on serial arterial blood sampling and cerebrospinal fluid. Muscle biopsy demonstrated cytochrome\u2010\n                    <jats:italic>c<\/jats:italic>\n                    oxidase\u2010positive \u2018ragged\u2010red\u2019 fibres consistent with MELAS; subsequent analyses revealed the m.3243A&gt;G point mutation most commonly associated with MELAS. The mutation was heteroplasmic, representing 92% of the total mtDNA from a lung sample. Nitric oxide and epoprostenol were administered without significant clinical or echocardiographic improvement of his PAH. A \u2018mitochondrial cocktail\u2019 including biotin, riboflavin, carnitine and coenzyme Q\n                    <jats:sub>10<\/jats:sub>\n                    also was provided. Five months after presentation, he developed seizures; MRI imaging of his brain demonstrated multiple focal lesions. His clinical status worsened with increasing cardiopulmonary failure. He died two months later. Although therapy for both MELAS and PAH remains limited, recent investigations suggest a beneficial role for l\u2010arginine in both conditions, implying a possible common pathophysiology. Mitochondrial diseases such as MELAS should be considered in cases of idiopathic PAH, particularly when associated with multisystem involvement including short stature, hearing loss, renal dysfunction, retinopathy, diabetes mellitus, migraines, seizures, ophthalmoplegia, fatigability and weakness.\n                  <\/jats:p>","DOI":"10.1007\/s10545-007-0735-3","type":"journal-article","created":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T06:04:19Z","timestamp":1199685859000},"page":"497-503","source":"Crossref","is-referenced-by-count":37,"title":["Pulmonary artery hypertension in a child with MELAS due to a point mutation of the mitochondrial tRNA\n                    <sup>(Leu)<\/sup>\n                    gene (m.3243A&gt;G)"],"prefix":"10.1002","volume":"31","author":[{"given":"D. M.","family":"Sproule","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology, Departments of Neurology and Pediatrics Columbia University Medical Center Harkness Pavilion, HP\u2010544, 180 Fort Washington Avenue New York NY 10032\u20103791 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dyme","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Hackensack University Medical Center Hackensack New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Coku","sequence":"additional","affiliation":[{"name":"H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"de Vinck","sequence":"additional","affiliation":[{"name":"Division of Pathology Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Children's Hospital of New York, Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics, Departments of Pediatrics and Medicine Columbia University Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. C.","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Departments of Neurology and Pediatrics Columbia University Medical Center Harkness Pavilion, HP\u2010544, 180 Fort Washington Avenue New York NY 10032\u20103791 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.4.955"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-4484-x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.609008"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1201\/b14623"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20598"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2006.02043.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389400900102"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(92)90045-8"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02258374"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)7:4<358::AID-HUMU11>3.0.CO;2-1"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000196641.05913.27"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000220197.36849.1e"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.8.654"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000145360.16770.9f"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200208-967OC"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","unstructured":"NainiA KaufmannP ShanskeS et al (2005)Hypocitrullinemia in patients with MELAS: an insight into the \u2018MELAS paradox\u2019.J Neurol Sci229\u2013230:187\u2013193.","DOI":"10.1016\/j.jns.2004.11.026"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.80.3.292"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160409"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-2-216"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199702273360902"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(94)90272-0"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003643-200403000-00002"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199702)20:2<221::AID-MUS13>3.0.CO;2-5"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1625"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000031098.41409.55"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000045711.89888.5e"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.7.607"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000244091"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00722.2004"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2317fje"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90136-D"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0735-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:29:55Z","timestamp":1694737795000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-007-0735-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,7]]},"references-count":31,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1007\/s10545-007-0735-3"],"URL":"https:\/\/doi.org\/10.1007\/s10545-007-0735-3","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,7]]}}}