The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency
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 h...
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MDPI AG
2021-10-01
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| author | Orna Staretz-Chacham Ben Pode-Shakked Eyal Kristal Smadar Yaala Abraham Keren Porper Ohad Wormser Ilan Shelef Yair Anikster |
| author_facet | Orna Staretz-Chacham Ben Pode-Shakked Eyal Kristal Smadar Yaala Abraham Keren Porper Ohad Wormser Ilan Shelef Yair Anikster |
| author_sort | Orna Staretz-Chacham |
| collection | DOAJ |
| description | 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’ 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. |
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| issn | 2072-6643 |
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| publishDate | 2021-10-01 |
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| series | Nutrients |
| spelling | doaj.art-41e458e5c11245b6b93cd887355b425e2023-11-22T19:29:52ZengMDPI AGNutrients2072-66432021-10-011310352310.3390/nu13103523The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase DeficiencyOrna Staretz-Chacham0Ben Pode-Shakked1Eyal Kristal2Smadar Yaala Abraham3Keren Porper4Ohad Wormser5Ilan Shelef6Yair Anikster7Metabolic Clinic, Soroka Medical Center, Beer Sheva 8480101, IsraelMetabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, IsraelFaculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, IsraelMetabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, IsraelMetabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, IsraelThe 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, IsraelFaculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, IsraelMetabolic Disease Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, IsraelBackground: 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’ 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.https://www.mdpi.com/2072-6643/13/10/3523dihydrolipoamide dehydrogenase (DLD)pyruvate dehydrogenase complex (PDHC)ketogenic diet |
| spellingShingle | Orna Staretz-Chacham Ben Pode-Shakked Eyal Kristal Smadar Yaala Abraham Keren Porper Ohad Wormser Ilan Shelef Yair Anikster The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency Nutrients dihydrolipoamide dehydrogenase (DLD) pyruvate dehydrogenase complex (PDHC) ketogenic diet |
| title | The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency |
| title_full | The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency |
| title_fullStr | The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency |
| title_full_unstemmed | The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency |
| title_short | The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency |
| title_sort | effects of a ketogenic diet on patients with dihydrolipoamide dehydrogenase deficiency |
| topic | dihydrolipoamide dehydrogenase (DLD) pyruvate dehydrogenase complex (PDHC) ketogenic diet |
| url | https://www.mdpi.com/2072-6643/13/10/3523 |
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