Department of Pediatrics, Taitung MacKay Memorial Hospital, Taitung, Taiwan.
Epilepsy Behav. 2023 Sep;146:109363. doi: 10.1016/j.yebeh.2023.109363. Epub 2023 Jul 25.
Lysine, as an essential amino acid, predominantly undergoes metabolic processes through the saccharopine pathway, whereas a smaller fraction follows the pipecolic acid pathway. Although the liver is considered the primary organ for lysine metabolism, it is worth noting that lysine catabolism also takes place in other tissues and organs throughout the body, including the brain. Enzyme deficiency caused by pathogenic variants in its metabolic pathway may lead to a series of neurometabolic diseases, among which glutaric aciduria type 1 and pyridoxine-dependent epilepsy have the most significant clinical manifestations. At present, through research, we have a deeper understanding of the multiple pathophysiological mechanisms related to these diseases, including intracerebral accumulation of neurotoxic metabolites, imbalance between GABAergic and glutamatergic neurotransmission, energy deprivation due to metabolites, and the dysfunction of antiquitin. Because of the complexity of these diseases, their clinical manifestations are also diverse. The early implementation of lysine-restricted diets and supplementation with arginine and carnitine has reported positive impacts on the neurodevelopmental outcomes of patients. Presently, there is more robust evidence supporting the effectiveness of these treatments in glutaric aciduria type 1 compared with pyridoxine-dependent epilepsy.
赖氨酸是一种必需氨基酸，主要通过 saccharopine 途径进行代谢，而一小部分则通过哌啶酸途径进行代谢。虽然肝脏被认为是赖氨酸代谢的主要器官，但值得注意的是，赖氨酸的分解代谢也发生在身体的其他组织和器官中，包括大脑。其代谢途径中的致病性变异导致的酶缺乏可能导致一系列神经代谢疾病，其中谷氨酸尿症 1 型和吡哆醇依赖性癫痫的临床表现最为显著。目前，通过研究，我们对与这些疾病相关的多种病理生理机制有了更深入的了解，包括脑内神经毒性代谢物的积累、GABA 能和谷氨酸能神经递质传递的失衡、代谢物引起的能量剥夺以及抗霉素的功能障碍。由于这些疾病的复杂性，它们的临床表现也多种多样。早期实施赖氨酸限制饮食并补充精氨酸和肉碱已报告对患者的神经发育结果有积极影响。目前，有更有力的证据支持这些治疗方法在谷氨酸尿症 1 型中的有效性，而不是吡哆醇依赖性癫痫。
