Khosravi Sepehr, Amini Elaheh, Emamikhah Maziar, Alavi Afagh, Lang Anthony E, Rohani Mohammad
Department of Neurology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Neurology, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.
Mov Disord Clin Pract. 2025 Jun;12(6):852-857. doi: 10.1002/mdc3.70027. Epub 2025 Mar 3.
Mutations in the ATP13A2 gene have been implicated in various neurodegenerative disorders, including Kufor-Rakeb syndrome (KRS), neuronal ceroid lipofuscinosis (NCL), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). This report presents two Iranian families with ATP13A2 variants exhibiting atypical features of KRS.
We highlight four patients from two consanguineous Iranian families with mutations in the ATP13A2 gene presenting with variable features of motor neuron disease as well as juvenile-onset parkinsonism, and cognitive decline. The onset of symptoms ranged from 11 to 29 years, with initial manifestations including gait disturbance, postural instability, and cognitive impairment. As the disease progressed, patients developed a range of neurological signs, such as dystonia, spasticity, and dysarthria.
This report expands the phenotypic spectrum of ATP13A2-related disorders, highlighting the potential overlap of symptoms associated with KRS, ALS, and HSP.
ATP13A2基因突变与多种神经退行性疾病有关，包括库福尔-拉凯布综合征（KRS）、神经元蜡样脂褐质沉积症（NCL）、遗传性痉挛性截瘫（HSP）和肌萎缩侧索硬化症（ALS）。本报告介绍了两个携带ATP13A2变异体的伊朗家族，这些变异体表现出KRS的非典型特征。
我们重点介绍了来自两个伊朗近亲家族的四名患者，他们的ATP13A2基因发生突变，表现出运动神经元疾病以及青少年型帕金森症和认知功能下降的多种特征。症状出现的年龄在11至29岁之间，最初表现包括步态障碍、姿势不稳和认知障碍。随着疾病进展，患者出现了一系列神经学体征，如肌张力障碍、痉挛和构音障碍。
本报告扩展了ATP13A2相关疾病的表型谱，突出了与KRS、ALS和HSP相关症状的潜在重叠。
