Metabolic Clinic, Soroka Medical Center, Beer Sheva 8480101, Israel.
Faculty of Health Sciences, Ben-Gurion University, Beer Sheva 8410501, Israel.
Nutrients. 2021 Oct 7;13(10):3523. doi: 10.3390/nu13103523.
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).
To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment.
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.
The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.
二氢硫辛酰胺脱氢酶（DLD 硫辛酰胺脱氢酶，丙酮酸脱氢酶复合物（PDHC）的 E3 亚基）是 PDHC 的第三个催化酶，它将丙酮酸转化为乙酰辅酶 A，同时引入乙酰辅酶 A 进入三羧酸（TCA）循环。在人类中，PDHC 在有氧、产生能量的过程中对维持葡萄糖内稳态起着重要作用。由 DLD 中的致病性变异引起的遗传性 DLD-E3 缺乏症导致疾病表现和病程的变化，从肌病、反复发作的肝病和呕吐到 Leigh 病和早逝不等。目前，虽然有人建议采用生酮饮食（KD），但尚无治疗指南的共识。
描述与标准治疗相比，KD 在 DLD-E3 缺乏症患者中的使用和效果。
共纳入 16 名患者。其中 8 名来自历史队列，另外 8 名中有 4 名接受部分 KD 治疗。所有患者均为 DLD 中 D479V（或 D444V，对应于没有线粒体靶向序列的成熟蛋白的突变体）致病性变异的纯合子。部分 KD 治疗被发现可提高患者生存率。然而，与历史队列相比，患者的生活质量（QOL）并没有显著改善。
KD 的使用在生存率方面具有优势；然而，在 QOL 方面没有显著改善。
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