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PODs are not only caused by deficiency of subunits of the pyruvate dehydrogenase complex (PDHC) but also by various disorders recently described in the whole pyruvate oxidation route including cofactors, regulation of PDHC and the mitochondrial pyruvate carrier. Our own patients from 2000 to July 2014 and patients identified by a systematic survey of the literature from 1970 to July 2014 with a pyruvate oxidation disorder and a genetically proven defect were included in the study (n=628). Of these defects 74.2% (n=466) belong to PDHC subunits, 24.5% (n=154) to cofactors, 0.5% (n=3) to PDHC regulation and 0.8% (n=5) to mitochondrial pyruvate import. PODs are underestimated in the field of mitochondrial diseases because not all diagnostic centres include biochemical investigations of PDHC in their routine analysis. Cofactor and transport defects can be missed, if pyruvate oxidation is not measured in intact mitochondria routinely. Furthermore deficiency of the X\u2010chromosomal PDHA1 can be biochemically missed depending on the X\u2010inactivation pattern. This is reflected by an increasing number of patients diagnosed recently by genetic high throughput screening approaches. PDHC deficiency including regulation and import affect mainly the glucose dependent central and peripheral nervous system and skeletal muscle. PODs with combined enzyme defects affect also other organs like heart, lung and liver. The spectrum of clinical presentation of PODs is still expanding. PODs are a therapeutically interesting group of mitochondrial diseases since some can be bypassed by ketogenic diet or treated by cofactor supplementation. PDHC kinase inhibition, chaperone therapy and PGC1\u03b1 stimulation is still a matter of further investigations.<\/jats:p>","DOI":"10.1007\/s10545-014-9787-3","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T11:10:06Z","timestamp":1418987406000},"page":"391-403","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["The spectrum of pyruvate oxidation defects in the diagnosis of mitochondrial disorders"],"prefix":"10.1002","volume":"38","author":[{"given":"Wolfgang","family":"Sperl","sequence":"first","affiliation":[{"name":"Department of Paediatrics Paracelsus Medical University, SALK Salzburg Salzburg 5020 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Fleuren","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Paracelsus Medical University, SALK Salzburg Salzburg 5020 Austria"},{"name":"Nijmegen Centre for Mitochondrial Disorders at the Department of Paediatrics Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Kreisklinikum Reutlingen Reutlingen 72764 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Helmholtz Zentrum M\u00fcnchen Neuherberg 85764 Germany"},{"name":"Institute of Human Genetics Technische Universit\u00e4t M\u00fcnchen Munich 81675 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Ribes","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme, Servei de Bioqu\u00edmica I Gen\u00e8tica Molecular Hospital Clinic, IDIBAPS, CIBERER C\/Mej\u00eda Lequerica s\/n Barcelona 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Paracelsus Medical University, SALK Salzburg Salzburg 5020 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Nijmegen Centre for Mitochondrial Disorders at the Department of Paediatrics Radboud University Nijmegen Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz A.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Paracelsus Medical University, SALK Salzburg Salzburg 5020 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Paracelsus Medical University, SALK Salzburg Salzburg 5020 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Rivera","sequence":"additional","affiliation":[{"name":"Metabolism &amp; 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