{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:21:07Z","timestamp":1791145267310,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2009,11,9]],"date-time":"2009-11-09T00:00:00Z","timestamp":1257724800000},"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>Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the <jats:italic>PDHA1<\/jats:italic> gene which encodes the E<jats:sub>1<\/jats:sub>\u03b1 subunit, with few cases of mutations in the genes for E<jats:sub>3<\/jats:sub>, E3BP (E<jats:sub>3<\/jats:sub> binding protein), E<jats:sub>2<\/jats:sub> and E<jats:sub>1<\/jats:sub>\u2010phosphatase being reported. Only seven patients with deficiency of the E<jats:sub>1<\/jats:sub>\u03b2 subunit have been described, with mutations in the <jats:italic>PDHB<\/jats:italic> gene in six of them. Clinically they presented with a non\u2010specific encephalomyopathy. We report two patients with new mutations in <jats:italic>PDHB<\/jats:italic> and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E<jats:sub>1<\/jats:sub> activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in <jats:italic>PDHA1<\/jats:italic> were excluded. Sequencing of <jats:italic>PDHB<\/jats:italic> revealed a homozygous point mutation (c.302T&gt;C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A&gt;G (p.M101V) and c.313G&gt;A (p.R105Q). All three mutations appear to destabilize the E<jats:sub>1<\/jats:sub> enzyme with a decrease of both E<jats:sub>1<\/jats:sub>\u03b1 and E<jats:sub>1<\/jats:sub>\u03b2 subunits in immunoblot analysis. To our knowledge, these patients with novel <jats:italic>PDHB<\/jats:italic> mutations are the first reported with Leigh syndrome.<\/jats:p>","DOI":"10.1007\/s10545-009-1343-1","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T00:59:07Z","timestamp":1258592347000},"page":"339-343","source":"Crossref","is-referenced-by-count":20,"title":["PDH E<sub>1<\/sub>\u03b2 deficiency with novel mutations in two patients with Leigh syndrome"],"prefix":"10.1002","volume":"32","author":[{"given":"E.","family":"Quintana","sequence":"first","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Paracelsus Medical University Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Garc\u00eda Silva","sequence":"additional","affiliation":[{"name":"Departamento de Pediatr\u00eda Unidad Pedi\u00e1trica de Enfermedades Raras. E. Mitocondriales y Metab\u00f3licas Hereditarias, Hospital 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Font","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Tortoledo","sequence":"additional","affiliation":[{"name":"Departamento de Pediatr\u00eda Unidad Pedi\u00e1trica de Enfermedades Raras. E. Mitocondriales y Metab\u00f3licas Hereditarias, Hospital 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Moliner","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ozaez","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lluch","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Cabello","sequence":"additional","affiliation":[{"name":"Departamento de Pediatr\u00eda Unidad Pedi\u00e1trica de Enfermedades Raras. E. Mitocondriales y Metab\u00f3licas Hereditarias, Hospital 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. R.","family":"Ricoy","sequence":"additional","affiliation":[{"name":"Departamento de Pediatr\u00eda Unidad Pedi\u00e1trica de Enfermedades Raras. E. Mitocondriales y Metab\u00f3licas Hereditarias, Hospital 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Paracelsus Medical University Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ribes","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Sperl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Paracelsus Medical University Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Briones","sequence":"additional","affiliation":[{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic Barcelona Spain"},{"name":"CIBER de Enfermedades Raras (CIBERER) Barcelona Spain"},{"name":"Consejo Superior de Investigaciones Cient\u00edficas Barcelona Spain"},{"name":"Institut de Bioqu\u00edmica Cl\u00ednica Barcelona Edificio Helios III, c\/Mejia Lequerica s\/n, 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.11.875"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1124-8"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(96)00058-6"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.03.007"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704748200"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)7:1<46::AID-HUMU6>3.0.CO;2-N"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.10.135"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.14.2227213"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340217"},{"key":"e_1_2_5_11_1","first-page":"2275","volume-title":"The metabolic and molecular bases of inherited disease","author":"Robinson BH","year":"2001"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01959401"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1343-1","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-009-1343-1","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1343-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:16:14Z","timestamp":1694747774000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-009-1343-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,9]]},"references-count":11,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1007\/s10545-009-1343-1"],"URL":"https:\/\/doi.org\/10.1007\/s10545-009-1343-1","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,9]]}}}