Clinical and genetic characteristics analysis of 18 children with infantile epileptic spasms syndrome associated with mitochondrial gene variants
10.3760/cma.j.cn112140-20250706-00587
- VernacularTitle:线粒体基因变异相关IESS患儿18例临床及遗传学特征分析
- Author:
Tenghui WU
1
;
Rong LI
1
;
Zou PAN
1
;
Zhanwei ZHANG
1
;
Jing PENG
1
Author Information
1. 中南大学湘雅医院儿科 湖南省儿童脑发育障碍性疾病临床医学研究中心，长沙 410008
- Publication Type:Journal Article
- Keywords:
Mitochondrial diseases;
Epilepsy;
Disease attributes;
Therapy
- From:
Chinese Journal of Pediatrics
2025;63(10):1097-1102
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants.Methods:A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed.Results:Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score).Conclusions:Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.
