{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:13:18Z","timestamp":1784308398658,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). Objective: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. Results: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients\u2019 quality of life (QOL) was not significantly improved. Conclusions: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.<\/jats:p>","DOI":"10.3390\/nu13103523","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"3523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-4909","authenticated-orcid":false,"given":"Orna","family":"Staretz-Chacham","sequence":"first","affiliation":[{"name":"Metabolic Clinic, Soroka Medical Center, Beer Sheva 8480101, Israel"},{"name":"Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-9629","authenticated-orcid":false,"given":"Ben","family":"Pode-Shakked","sequence":"additional","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Kristal","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, Israel"},{"name":"Pediatric Ambulatory Day Unit, Soroka Medical Center, Beer Sheva 8480101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smadar Yaala","family":"Abraham","sequence":"additional","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-7536","authenticated-orcid":false,"given":"Keren","family":"Porper","sequence":"additional","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Wormser","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-6455","authenticated-orcid":false,"given":"Ilan","family":"Shelef","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, Israel"},{"name":"Department of Radiology, Soroka University Medical Center, Beer Sheva 8480101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[{"name":"Metabolic Disease Unit, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel"},{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1096\/fasebj.4.14.2227213","article-title":"Molecular Biology and Biochemistry of pyruvate dehydrogenase complexes","volume":"4","author":"Roche","year":"1990","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1002\/ajmg.a.31313","article-title":"Novel Mutations in Dihydrolipoamide Dehydrogenase Deficiency in Two Cousins with Borderline-Normal PDH Complex Activity","volume":"140","author":"Cameron","year":"2006","journal-title":"Am. 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