Jiang Huafang, Xu Chaolong, Liu Zhimei, Duan Ruoyu, Yao Xingfeng, Fu Xiaona, Xu Jiatong, Kang Xuejing, Yu Tenghui, Wang Yuanyuan, Fang Fang
Department of Pediatrics, Weifang Maternal and Child Health Hospital, Peking University Health Science Center-Weifang Joint Research Center for Maternal and Child Health, Weifang, China.
Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Pediatr. 2025 Sep 12;13:1608840. doi: 10.3389/fped.2025.1608840. eCollection 2025.
The gene encodes the E4 subunit of the 2-oxoglutarate dehydrogenase complex (OGDHC), a critical enzyme in the tricarboxylic acid cycle. OGDHC deficiency can lead to metabolic disorders with a clinical spectrum ranging from fatal neonatal lactic acidosis to variable degrees of global developmental delay and movement disorders. To date, a homozygous variant has been reported as a novel cause of Leigh syndrome in only two siblings, who presented with developmental delay, movement disorders, bilateral striatal necrosis, and reduced OGDHC activity.
We report a third case of Leigh syndrome associated with variants in a 2-year-old boy. The patient exhibited with global developmental delay, dystonia, early-onset chorea, and elevated serum lactate levels. Follow-up brain magnetic resonance imaging at 2 years revealed progressive degenerative lesions in the bilateral basal ganglia. Muscle biopsy showed abnormal mitochondrial accumulation beneath the sarcolemma, and the oxygen consumption rate was reduced in skin fibroblasts. Whole-exome sequencing identified two novel compound heterozygous variants: c.42+1G>A (p.?) and c.296G>C (p.Arg99Pro).
This case supports as a novel pathogenic cause of Leigh syndrome, further expanding the genetic spectrum of the disorder. Key clinical features include developmental delay, involuntary movement disorders, progressive basal ganglia atrophy, and a slowly progressive disease course.
该基因编码2-氧代戊二酸脱氢酶复合体（OGDHC）的E4亚基，这是三羧酸循环中的一种关键酶。OGDHC缺乏可导致代谢紊乱，临床症状范围从致命的新生儿乳酸酸中毒到不同程度的全面发育迟缓及运动障碍。迄今为止，仅在两名患有发育迟缓、运动障碍、双侧纹状体坏死和OGDHC活性降低的兄弟姐妹中报道了一种纯合变异作为Leigh综合征的新病因。
我们报告了一名2岁男孩中与该变异相关的Leigh综合征的第三例病例。该患者表现为全面发育迟缓、肌张力障碍、早发性舞蹈症和血清乳酸水平升高。2岁时的随访脑磁共振成像显示双侧基底神经节有进行性退行性病变。肌肉活检显示肌膜下线粒体异常积聚，皮肤成纤维细胞的氧消耗率降低。全外显子组测序鉴定出两个新的复合杂合变异：c.42+1G>A（p.?）和c.296G>C（p.Arg99Pro）。
该病例支持该变异作为Leigh综合征的一种新的致病原因，进一步扩展了该疾病的遗传谱。关键临床特征包括发育迟缓、不自主运动障碍、进行性基底神经节萎缩和缓慢进展的病程。
