The use of sodium DL-3-Hydroxybutyrate in severe acute neuro-metabolic compromise in patients with inherited ketone body synthetic disorders
The use of sodium DL-3-Hydroxybutyrate in severe acute neuro-metabolic compromise in patients with inherited ketone body synthetic disorders
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DOI：
10.1186/s13023-020-1316-x
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发表时间：
2020-02-18
影响因子：
3.7
通讯作者：
Tchan, Michel
中科院分区：
文献类型：
--
作者：
Bhattacharya, Kaustuv;Matar, Walid;Tchan, Michel
背景技术酮体在各种生理环境下形成终末器官的重要能量来源。在不同的时间，心脏、大脑和骨骼肌尤其可以使用酮作为主要底物。在这种情况下无法产生酮会导致能量输送受损、严重的终末器官功能障碍甚至可能死亡。一系列先天性代谢缺陷 (IEM) 会以这种方式影响酮体的产生，包括肉碱转运至线粒体的障碍、线粒体脂肪酸氧化缺陷 (MFAOD) 和酮体合成。在严重能量缺乏的情况下，IEM 的管理通常需要通过补充能量需求来避免酶缺乏。由于严重的多器官衰竭，在这种情况下通常很难提供最佳的肠内治疗，如本文所述，在这些情况下已尝试使用 DL-3-羟基丁酸钠 (S DL-3-OHB) 进行救援。结果 我们提出了 3 例代谢失代偿病例，其中一例患有肉碱酰基肉碱转位酶缺陷 (CACTD)，另一例患有 3-羟基、3-甲基、戊二酰辅酶 A 裂解酶缺陷 (HMGCLD)，第三例患有肉碱棕榈酰转移酶 II 缺陷 (CPT2D)。在发生灾难性的急性代谢恶化的情况下，所有这些疾病常常与死亡相关。辅助 S DL-3OHB 强化治疗使所有人快速持续康复。在这些情况下，替代疗法很少见。结论 S DL-3-OHB 已用于治疗急性神经和心脏损害的多酰基辅酶 A 脱氢酶缺乏症 (MADD) 病例，长期数据有待发表。 S DL-3-OHB 在非 MADD 脂肪氧化障碍中的应用是新颖的，并有助于更广泛使用的争论。
Background Ketone bodies form a vital energy source for end organs in a variety of physiological circumstances. At different times, the heart, brain and skeletal muscle in particular can use ketones as a primary substrate. Failure to generate ketones in such circumstances leads to compromised energy delivery, critical end-organ dysfunction and potentially death. There are a range of inborn errors of metabolism (IEM) affecting ketone body production that can present in this way, including disorders of carnitine transport into the mitochondrion, mitochondrial fatty acid oxidation deficiencies (MFAOD) and ketone body synthesis. In situations of acute energy deficit, management of IEM typically entails circumventing the enzyme deficiency with replenishment of energy requirements. Due to profound multi-organ failure it is often difficult to provide optimal enteral therapy in such situations and rescue with sodium DL-3-hydroxybutyrate (S DL-3-OHB) has been attempted in these conditions as documented in this paper. Results We present 3 cases of metabolic decompensation, one with carnitine-acyl-carnitine translocase deficiency (CACTD) another with 3-hydroxyl, 3-methyl, glutaryl CoA lyase deficiency (HMGCLD) and a third with carnitine palmitoyl transferase II deficiency (CPT2D). All of these disorders are frequently associated with death in circumstance where catastrophic acute metabolic deterioration occurs. Intensive therapy with adjunctive S DL-3OHB led to rapid and sustained recovery in all. Alternative therapies are scarce in these situations. Conclusion S DL-3-OHB has been utilised in multiple acyl co A dehydrogenase deficiency (MADD) in cases with acute neurological and cardiac compromise with long-term data awaiting publication. The use of S DL-3-OHB is novel in non-MADD fat oxidation disorders and contribute to the argument for more widespread use.