{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:46:06Z","timestamp":1792050366902,"version":"4.4.0"},"reference-count":11,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2009,6,11]],"date-time":"2009-06-11T00:00:00Z","timestamp":1244678400000},"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":[[2009,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The pyruvate dehydrogenase (PDH) complex is a mitochondrial multienzyme that catalyses the irreversible oxidative decarboxylation of pyruvate to acetyl\u2010CoA. We report four novel <jats:italic>PDHA1<\/jats:italic> mutations in patients with pyruvate dehydrogenase deficiency. Analysis of PDH activity showed decreased activity in fibroblasts from all four patients, around 16\u201352% of mean control, similar to what has been found in previous studies. Two of the mutations were missense mutations: c.616G&gt;A (p.Glu206Lys) and c.457A&gt;G (p.Met153Val), one was a 3 bp in\u2010frame deletion: c.429_431delAGG (p.Gly143del), and one was a 65 bp duplication: c.900\u20136_958dup65. cDNA analysis of the 65 bp duplication showed a small amount of normal transcript in addition to the transcript corresponding to the duplication. The small amount of normal transcript likely explains the survival of the patient, who was a boy. The duplication and one of the missense mutations were associated with decreased amounts of E<jats:sub>1<\/jats:sub>\u03b1 And E<jats:sub>1<\/jats:sub>\u03b2 protein on western blot analysis, whereas the other two mutations were associated with normal amounts. This study adds four novel mutations to the around 90 reported mutations in <jats:italic>PDHA1<\/jats:italic> (HGMD <jats:italic>PDHA1<\/jats:italic> mutation database). The phenotypes of patients with PDH deficiency have been divided into three groups: a neonatal form with severe lactic acidosis, a form observed only in males and characterized by episodes of ataxia with relapses associated with hyperlactataemia, and an infantile form with hypotonia, lethargy, onset of seizures or dystonia, psychomotor retardation, in some cases Leigh\u2010like lesions and mild to moderate hyperlactataemia. The four patients reported here all belong to the latter group, which is the largest.<\/jats:p>","DOI":"10.1007\/s10545-009-1179-8","type":"journal-article","created":{"date-parts":[[2009,6,10]],"date-time":"2009-06-10T15:43:32Z","timestamp":1244648612000},"page":"235-239","source":"Crossref","is-referenced-by-count":10,"title":["Four novel <i>PDHA1<\/i> mutations in pyruvate dehydrogenase deficiency"],"prefix":"10.1002","volume":"32","author":[{"given":"E.","family":"Ostergaard","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics 4062 Copenhagen University Hospital Rigshospitalet Blegdamsvej 9 Copenhagen 2100 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Birk","family":"Moller","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory, Kennedy Center Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Serap","family":"Kalkanoglu\u2010Sivri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition &amp; Metabolism Hacettepe University Faculty of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dursun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition &amp; Metabolism Hacettepe University Faculty of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kibaek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Thelle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Viborg Hospital Viborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics 4062 Copenhagen University Hospital Rigshospitalet Blegdamsvej 9 Copenhagen 2100 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Duno","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics 4062 Copenhagen University Hospital Rigshospitalet Blegdamsvej 9 Copenhagen 2100 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Wibrand","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics 4062 Copenhagen University Hospital Rigshospitalet Blegdamsvej 9 Copenhagen 2100 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1124-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30287"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20550"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1995.1523"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200003)15:3<209::AID-HUMU1>3.0.CO;2-K"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.11.5186"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0123"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1204"},{"key":"e_1_2_6_10_1","first-page":"2275","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Robinson BH","year":"2001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000468654"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(69)13005-0"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1179-8","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-009-1179-8","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1179-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:18:09Z","timestamp":1694747889000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-009-1179-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,11]]},"references-count":11,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1007\/s10545-009-1179-8"],"URL":"https:\/\/doi.org\/10.1007\/s10545-009-1179-8","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,11]]}}}