Yano Sho T, Silver Kenneth, Young Richard, DeBrosse Suzanne D, Ebel Roseànne S, Swoboda Kathryn J, Acsadi Gyula
Section of Pediatric Neurology, Comer Children's Hospital, University of Chicago, Chicago, Illinois.
Section of Pediatric Neurology, Comer Children's Hospital, University of Chicago, Chicago, Illinois.
Pediatr Neurol. 2017 Aug;73:101-105. doi: 10.1016/j.pediatrneurol.2017.04.022. Epub 2017 Apr 29.
We identified a group of patients with ATP1A3 mutations at residue 756 who display a new phenotype, distinct from alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndromes.
Four patients with c.2267G>A (R756H) mutations from two families and two patients with c.2267G>T (R756L) mutations from one family are described and compared with the previously reported patients with mutations resulting in R756H and R756C protein variants.
Patients with ATP1A3 R756H have onset in childhood of infrequent, fever-triggered paroxysms of encephalopathy and weakness with slowly improving but persistent deficits. Motor findings of weakness are mostly generalized, and patients may also have bulbar or oculomotor problems. Longer-term outcomes range from mild motor apraxia with near-normal function to persistent dysphagia, dysarthria, cognitive deficit, motor apraxia, and inability to walk because of ataxia. Patients with ATP1A3 R756L have a similar phenotype that includes paroxysmal, stepwise progression of ataxia associated with infections.
ATP1A3 mutations affecting residue 756 result in a clinical syndrome, separate from those associated with previously described ATP1A3 mutations, which consists chiefly of fever-induced paroxysmal weakness and encephalopathy (FIPWE). Patients with R756L and R756C protein variants display more prominent ataxia, overlapping with the relapsing encephalopathy with cerebellar ataxia syndrome previously described in a patient with the c.2266C>T (R756C) mutation. All patients reported with mutations at residue 756 to date have had a similar episodic course and clinical features. Patients with mutations of ATP1A3 residue 756 appear to have a distinct clinical phenotype compared with patients with other ATP1A3 mutations, with fever-induced encephalopathy as key differentiating feature.
我们鉴定出一组在第756位残基处存在ATP1A3突变的患者，他们表现出一种新的表型，不同于儿童交替性偏瘫、快速进展性肌张力障碍-帕金森综合征以及小脑共济失调、无反射、高弓足、视神经萎缩、感音神经性听力损失综合征。
描述了来自两个家族的4例携带c.2267G>A（R756H）突变的患者以及来自一个家族的2例携带c.2267G>T（R756L）突变的患者，并与先前报道的携带导致R756H和R756C蛋白变体突变的患者进行比较。
携带ATP1A3 R756H突变的患者在儿童期起病，表现为不频繁的、发热诱发的脑病和肌无力发作，症状缓慢改善但遗留持续缺陷。肌无力的运动表现大多为全身性，患者还可能有延髓或动眼神经问题。长期预后范围从功能接近正常的轻度运动失用到持续的吞咽困难、构音障碍、认知缺陷、运动失用以及因共济失调而无法行走。携带ATP1A3 R756L突变的患者具有相似的表型，包括与感染相关的发作性、进行性共济失调。
影响第756位残基的ATP1A3突变导致一种临床综合征，与先前描述的ATP1A3突变相关的综合征不同，主要由发热诱导的阵发性肌无力和脑病（FIPWE）组成。携带R756L和R756C蛋白变体的患者表现出更明显的共济失调，与先前在一名携带c.2266C>T（R756C）突变的患者中描述的复发性脑病伴小脑共济失调综合征重叠。迄今为止报道的所有在第756位残基处存在突变的患者都有相似的发作病程和临床特征。与其他ATP1A3突变的患者相比，携带ATP1A3第756位残基突变的患者似乎具有独特的临床表型，发热诱导的脑病是关键的鉴别特征。
