{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:19:09Z","timestamp":1781846349786,"version":"3.54.5"},"reference-count":11,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T00:00:00Z","timestamp":1248825600000},"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>Pyruvate dehydrogenase (PDH) is a crucial multienzyme system linking glycolysis to the tricarboxylic acid cycle by catalysing the decarboxylation of pyruvate to acetyl\u2010CoA. Deficiency in pyruvate dehydrogenase is most commonly secondary to mutations in the X\u2010linked <jats:italic>PDHA1<\/jats:italic> gene encoding the E1 alpha subunit. There is a wide range of clinical presentations from severe neonatal lactic acidosis to chronic encephalopathy (Leigh syndrome). In recent years, a small subset of patients was recognized with less severe involvement, presenting initially only with intermittent symptoms, mainly of ataxia. Most of these patients remain stable for a number of years before developing progressive neurological deterioration around puberty at the latest. There does not appear to be a reliable correlation between genotype, phenotype, or enzyme activity. This makes counselling in a clinical setting challenging. We report a case with a previously known common mutation in PDHA1 (R263G) with an excellent outcome at 18 years of age. Previous patients with this mutation have presented with mental retardation and\/or Leigh syndrome, while our patient's clinical outcome is exceptional. He is cognitively normal and has normal brain MRI. His management includes a stringent carbohydrate\u2010free diet, as well as supplementation with thiamine, carnitine and vitamin E. This case further broadens the clinical spectrum, including now an example of a cognitively normal adult with PDH deficiency.<\/jats:p>","DOI":"10.1007\/s10545-009-1101-4","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T16:48:09Z","timestamp":1248799689000},"page":"123-126","source":"Crossref","is-referenced-by-count":8,"title":["A cognitively normal PDH\u2010deficient 18\u2010year\u2010old man carrying the R263G mutation in the <i>PDHA1<\/i> gene"],"prefix":"10.1002","volume":"32","author":[{"given":"R.","family":"Bachmann\u2010Gagescu","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine University of Washington School of Medicine Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"J. Lawrence","family":"Merritt","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine Seattle WA USA"},{"name":"Biochemical Genetics Program, Department of Pediatrics, Division of Genetic Medicine University of Washington School of Medicine, Seattle Children's Hospital B6594 4800 Sand Point Way Seattle WA 98105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,29]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30287"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.4.449"},{"key":"e_1_2_4_4_1","first-page":"558","article-title":"Mutations in the X\u2010linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex","volume":"56","author":"Chun K","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1077084"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198807000-00022"},{"key":"e_1_2_4_7_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_4_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050449"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005305614374"},{"key":"e_1_2_4_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(02)00187-9"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(87)80112-9"},{"key":"e_1_2_4_12_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199208000-00009"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1101-4","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-009-1101-4","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-009-1101-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:17:21Z","timestamp":1694747841000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-009-1101-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,29]]},"references-count":11,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1007\/s10545-009-1101-4"],"URL":"https:\/\/doi.org\/10.1007\/s10545-009-1101-4","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,29]]}}}