{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:58:55Z","timestamp":1770825535523,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2006,6,12]],"date-time":"2006-06-12T00:00:00Z","timestamp":1150070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2006,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have diagnosed dihydrolipoamide dehydrogenase (DLD) deficiency in two male second cousins, who presented with markedly different clinical phenotypes. Patient 1 had a recurrent encephalopathy, and patient 2 had microcephaly and lactic acidosis. Their presentation is unusual, in that the DLD subunit deficiency had little effect on pyruvate dehydrogenase complex activity, but caused a severe reduction in the activities of other enzymes that utilize this subunit. We have identified two mutations in the <jats:italic>DLD<\/jats:italic> gene in each patient. The second cousins have one novel mutation in common resulting in a substitution of isoleucine for threonine (I47T), which has not been previously reported in the literature. Patient 1 has a second mutation that has been reported to be common in the Ashkenazi Jewish population, G229C. Patient 2 has a second mutation, E375K, which has also been previously reported in the literature. Enzyme kinetic measurements on patient fibroblasts show that under certain conditions, one heteroallelic mutation may have a higher K<jats:sub>m<\/jats:sub>. This may account for the differing clinical phenotypes. These findings have important repercussions for other patients with similar clinical phenotypes, as DLD activity is not normally measured in cases with normal PDHc activity. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31313","type":"journal-article","created":{"date-parts":[[2006,6,13]],"date-time":"2006-06-13T03:32:09Z","timestamp":1150169529000},"page":"1542-1552","source":"Crossref","is-referenced-by-count":52,"title":["Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline\u2010normal PDH complex activity"],"prefix":"10.1002","volume":"140A","author":[{"given":"Jessie M.","family":"Cameron","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy","family":"Levandovskiy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neviana","family":"MacKay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Raiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah L.","family":"Renaud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe T.R.","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Feigenbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orly","family":"Elpeleg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian H.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,12]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1319","article-title":"Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency","volume":"7","author":"Cerna L","year":"2001","journal-title":"Med Sci Monit"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-003-1282-z"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.1925"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(97)00073-2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000010004.12053.5b"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.11.5186"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.26.15545"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0123"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9319"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bmme.1996.0078"},{"key":"e_1_2_8_12_1","first-page":"153","volume-title":"Mitochondira: A practical approach","author":"Robinson BH","year":"1987"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198008000-00013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990115)82:2<177::AID-AJMG15>3.0.CO;2-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1133"},{"key":"e_1_2_8_16_1","first-page":"79","volume-title":"Inborn errors of metabolism Part 2: Laboratory methods","author":"Yi\u2010Yung DI","year":"1967"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.31313","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.31313","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T20:12:59Z","timestamp":1696968779000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.31313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,12]]},"references-count":15,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2006,7,15]]}},"alternative-id":["10.1002\/ajmg.a.31313"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.31313","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,12]]}}}