Analysis of clinical and genetic characteristics of patients with relapsing encephalopathy with cerebellar ataxia caused by ATP1A3 gene R756 variants
10.3760/cma.j.cn113694-20250819-00489
- VernacularTitle:ATP1A3基因R756变异导致的复发性脑病伴小脑共济失调患者临床及遗传学特点分析
- Author:
Shupin LI
1
;
Xiaoling YANG
;
Miaomiao CHENG
;
Ting WANG
;
Shijia OUYANG
;
Ying YANG
;
Jing ZHANG
;
Aijie LIU
;
Qian CHEN
;
Yuehua ZHANG
Author Information
1. 首都医科大学附属首都儿童医学中心癫痫中心，北京100020
- Publication Type:Journal Article
- Keywords:
Gene;
Ataxia;
Encephalopathy;
ATP1A3 gene
- From:
Chinese Journal of Neurology
2025;58(12):1293-1300
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical phenotype and genetic features of patients with relapsing encephalopathy with cerebellar ataxia (RECA) caused by ATP1A3 gene R756 variants. Methods:A retrospective analysis was performed on patients carrying the ATP1A3 gene R756 variants, identified by whole-exome sequencing of family members, at Capital Center for Children′s Health, Capital Medical University and Children's Medical Center, Peking University First Hospital from August 2005 to February 2024. Their clinical, laboratory, neuroimaging, electrophysiological and genetic characteristics were summarized. Results:A total of 13 RECA patients were enrolled in this study, including 8 males and 5 females. The age of onset was 8 months to 5 years, with a median age of onset of 18 months. All of 13 patients presented paroxysmal episodes of neurological decompensations triggered by fever and residual symptoms following the acute phase. During acute attack stage, ataxia was observed in all 13 cases, muscle weakness in 12 cases, dysarthria in 12 cases, altered consciousness in 10 cases, dysphagia in 10 cases, dystonic episodes in 4 cases, abnormal eye movement in 2 cases, choreoathetosis in 2 cases, and epileptic seizures in 1 case. All 13 patients had residual symptoms during the nonparoxysmal period, of whom 9 patients had ataxia, 9 patients had dysarthria, 4 patients had dystonia, 3 patients had cognitive disorders, and 1 patient had epileptic seizures. All 13 cases had ATP1A3 missense variants, and variant c.2266C>T/p.R756C was found in 6 cases, c.2267G>A/p.R756H in 5 cases, and c.2267G>T/p.R756L in 2 cases. Nine cases carried de novo variants, 4 with inherited variants. Conclusions:RECA caused by variants of ATP1A3 in residue 756 typically presents with an acute onset during infancy or early childhood, precipitated by febrile episodes and characterized by recurrent episodes of ataxia, with bulbar paralysis, muscle weakness and altered consciousness. Recurrence is common, and the most common persistent symptoms are cerebellar ataxia and dysarthria. A few patients have cognitive impairment. Three types of ATP1A3 gene variants R756C, R756H and R756L are related with RECA, and R756C is the most common variant.
