本研究的目的是研究表型,基因型,治疗策略,中国西南地区ATP1A3(Na+/K+-ATPaseα3基因)相关疾病患儿的短期预后。2015年12月至2019年5月,在重庆医科大学儿童医院注册了使用下一代测序鉴定的致病性ATP1A3变异的患者。我们跟踪他们作为一个队列,并分析他们的临床数据。11例患者被鉴定为从头致病性ATP1A3杂合变体。一个(c.2542+1G>T,剪接)尚未报道。8名儿童交替偏瘫患者(AHC),一个小脑共济失调,无反射,pescavus,视神经萎缩,和感音神经性听力损失(CAPOS),包括2例复发性脑病伴小脑共济失调(RECA)。AHC的最初表现包括偏瘫,动眼异常,和癫痫发作,最常见的诱因是无发热的上呼吸道感染。所有患者在病程中均有阵发性偏瘫发作。脑部MRI未见异常。八个AHC病例中有六个在治疗后达到稳定的疾病状态。CAPOS患者的最初症状是共济失调,然后是发育消退,癫痫发作,耳聋,视力障碍,和构音障碍,脑部MRI显示轻度小脑萎缩.在使用乙酰唑胺后没有观察到波动。两例RECA患者最初表现为肌张力障碍和脑病,分别。一种表现为由发烧引发的肌张力障碍的快速发作过程,然后是构音障碍和动作震颤,独立行走是不可能的。脑部MRI图像正常。另一个出现意识障碍,癫痫发作,睡眠障碍,震颤,和运动障碍。脑电图显示背景缓慢(δ活动),脑MRI结果正常.他们没有注意到对氟桂利嗪的反应,他们需要61和60个月才能达到稳定的疾病状态,分别。
结论:致病性ATP1A3变异体在钠-钾泵疾病的发病机制中起重要作用,AHC是最常见的表型。治疗策略和预后取决于由不同变异部位和类型引起的表型类别。基因型和表型之间的相关性需要进一步探索。
背景:•致病杂合ATP1A3变异导致一系列神经表型,和ATP1A3障碍被视为具有非典型和重叠特征的表型连续体。•ATP1A3疾病的基因型-表型相关性仍不清楚。
背景:•在这项研究中,描述了中国西南地区ATP1A3相关疾病的基因型和表型。在ATP1A3相关疾病中首次检测到剪接位点变异c.2542+1G>T。•AHCp.Gly947Arg双胞胎的预后比具有其他变异的AHC病例更严重,这与以前的报告不一致。该现象表明基因型和表型之间相关性的多样性。
The aim of this research is to study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with
ATP1A3 (Na+/K+-ATPase alpha 3 gene)-related disorders in Southwest China. Patients with pathogenic
ATP1A3 variants identified using next-generation sequencing were registered at the Children\'s Hospital of Chongqing Medical University from December 2015 to May 2019. We followed them as a cohort and analyzed their clinical data. Eleven patients were identified with de novo pathogenic
ATP1A3 heterozygous variants. One (c.2542 + 1G > T, splicing) has not been reported. Eight patients with alternating hemiplegia of childhood (AHC), one with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), and two with relapsing encephalopathy with cerebellar ataxia (RECA) were included. The initial manifestations of AHC included hemiplegia, oculomotor abnormalities, and seizures, and the most common trigger was an upper respiratory tract infection without fever. All patients had paroxysmal hemiplegic attacks during their disease course. The brain MRI showed no abnormalities. Six out of eight AHC cases reached a stable disease state after treatment. The initial symptom of the patient with CAPOS was ataxia followed by developmental regression, seizures, deafness, visual impairment, and dysarthria, and the brain MRI indicated mild cerebellar atrophy. No fluctuation was noted after using Acetazolamide. The initial manifestations of the two RECA cases were dystonia and encephalopathy, respectively. One manifested a rapid-onset course of dystonia triggered by a fever followed by dysarthria and action tremors, and independent walking was impossible. The brain MRI image was normal. The other one presented with disturbance of consciousness, seizures, sleep disturbance, tremor, and dyskinesias. The EEG revealed a slow background (δ activity), and the brain MRI result was normal. No response to Flunarizine was noted for them, and it took 61 and 60 months for them to reach a stable disease state, respectively.
CONCLUSIONS: Pathogenic ATP1A3 variants play an essential role in the pathogenesis of Sodium-Potassium pump disorders, and AHC is the most common phenotype. The treatment strategies and prognosis depend on the phenotype categories caused by different variation sites and types. The correlation between the genotype and phenotype requires further exploration.
BACKGROUND: • Pathogenic heterozygous ATP1A3 variants cause a spectrum of neurological phenotypes, and
ATP1A3-disorders are viewed as a phenotypic continuum presenting with atypical and overlapping features. • The genotype-phenotype correlation of
ATP1A3-disorders remains unclear.
BACKGROUND: • In this study, the genotypes and phenotypes of ATP1A3-related disorders from Southwest of China were described. The splice-site variation c.2542+1G>T was detected for the first time in ATP1A3-related disorders. • The prognosis of twins with AHC p. Gly947Arg was more serious than AHC cases with other variants, which was inconsistent with previous reports. The phenomenon indicated the diversity of the correlation between the genotype and phenotype.