Magro Giuseppe, Laterza Vincenzo, Tosto Federico
Department of Neuroscience, "Giovanni Paolo II" Hospital, 88100 Lamezia Terme, Italy.
Department of Medical and Surgical Sciences, Institute of Neurology, Magna Graecia University, 88100 Catanzaro, Italy.
Biomedicines. 2025 Mar 17;13(3):733. doi: 10.3390/biomedicines13030733.
Leigh syndrome (LS) is a severe neurodegenerative condition with an early onset, typically during early childhood or infancy. The disorder exhibits substantial clinical and genetic diversity. From a clinical standpoint, Leigh syndrome showcases a broad range of irregularities, ranging from severe neurological issues to minimal or no discernible abnormalities. The central nervous system is most affected, resulting in psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure. Some patients also experience involvement of the peripheral nervous system, such as polyneuropathy or myopathy, as well as non-neurological anomalies, such as diabetes, short stature, hypertrichosis, cardiomyopathy, anemia, renal failure, vomiting, or diarrhea (Leigh-like syndrome). Mutations associated with Leigh syndrome impact genes in both the mitochondrial and nuclear genomes. Presently, LS remains without a cure and shows limited response to various treatments, although certain case reports suggest potential improvement with supplements. Ongoing preclinical studies are actively exploring new treatment approaches. This review comprehensively outlines the genetic underpinnings of LS, its current treatment methods, and preclinical investigations, with a particular focus on treatment.
Leigh综合征（LS）是一种严重的神经退行性疾病，起病较早，通常在幼儿期或婴儿期发病。该疾病表现出显著的临床和遗传多样性。从临床角度来看，Leigh综合征呈现出广泛的异常情况，从严重的神经问题到轻微或无明显异常。中枢神经系统受影响最大，导致精神运动发育迟缓、癫痫发作、眼球震颤、眼肌麻痹、视神经萎缩、共济失调、肌张力障碍或呼吸衰竭。一些患者还会出现周围神经系统受累，如多发性神经病或肌病，以及非神经异常，如糖尿病、身材矮小、多毛症、心肌病、贫血、肾衰竭、呕吐或腹泻（类Leigh综合征）。与Leigh综合征相关的突变会影响线粒体和核基因组中的基因。目前，LS仍然无法治愈，对各种治疗的反应有限，尽管某些病例报告表明补充剂可能会有所改善。正在进行的临床前研究正在积极探索新的治疗方法。本综述全面概述了LS的遗传基础、当前的治疗方法以及临床前研究，特别关注治疗方面。
