Nandana Jayakumari, Fasaludeen Alfiya, Kumar Adarsh Anil, Vijayaraghavan Asish, Nair Sruthi S, Cherian Ajith, Menon Ramshekhar N, Sundaram Soumya
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.
Cerebellum. 2025 Jun 10;24(4):112. doi: 10.1007/s12311-025-01866-3.
Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an exceptionally rare autosomal recessive neurodegenerative disorder. It is caused by biallelic inactivating variants in the ADP-ribosyl-serine hydrolase (ADPRS) gene that encodes for the enzyme ADP-ribosyl hydrolase3 (ARH3) involved in DNA repair. A distinctive feature of this condition is the exacerbation of clinical symptoms triggered by physical or emotional stress, as well as febrile illnesses. In this report, we describe three unrelated patients diagnosed with CONDSIAS, each having variable clinical phenotypes and responses to treatment. Patient 1 is a 26-year-old female with language delay, intellectual disability, and infrequent seizures in childhood. She later developed parkinsonism, truncal dystonia, ataxia, peripheral neuropathy, and neuropsychiatric symptoms in her second decade. Patient 2, an 8-year-old boy born to consanguineous parents, presented with infection-triggered episodic ataxia and ichthyosis. His elder sibling had suffered from progressive ataxia and succumbed to sudden death at the age of 8. Patient 3 is a 6-year-old girl who presented with progressive ataxia, myoclonus, oculomotor apraxia, and upward gaze palsy. Both patients 2 and 3 responded favourably to treatment with high-dose vitamin supplementation, while patient 1 showed stable disease progression without specific therapeutic intervention, suggesting spontaneous stabilization of her condition. Extra-neurological manifestations included ichthyosis in patients 1 and 2 and cataracts in patient 1. These three cases illustrate the heterogeneity in clinical presentation and prognosis of CONDSIAS, highlighting the occurrence of predominant extrapyramidal features and systemic involvement, thereby expanding the phenotypic spectrum beyond the typical manifestations of ataxia and seizures.
应激诱导的儿童期起病的神经退行性变伴可变共济失调和癫痫（CONDSIAS）是一种极其罕见的常染色体隐性神经退行性疾病。它由ADP-核糖基丝氨酸水解酶（ADPRS）基因的双等位基因失活变异引起，该基因编码参与DNA修复的酶ADP-核糖水解酶3（ARH3）。这种疾病的一个显著特征是身体或情绪应激以及发热性疾病引发临床症状的加重。在本报告中，我们描述了三名被诊断为CONDSIAS的非亲缘患者，他们各自具有可变的临床表型和对治疗的反应。患者1是一名26岁女性，童年时有语言发育迟缓、智力障碍和偶发癫痫。她在第二个十年后期出现帕金森综合征、躯干肌张力障碍、共济失调、周围神经病变和神经精神症状。患者2是一名8岁男孩，其父母为近亲结婚，表现为感染诱发的发作性共济失调和鱼鳞病。他的哥哥曾患有进行性共济失调，并在8岁时猝死。患者3是一名6岁女孩，表现为进行性共济失调、肌阵挛、眼球运动失用和向上凝视麻痹。患者2和3对高剂量维生素补充治疗反应良好，而患者1在没有特定治疗干预的情况下疾病进展稳定，提示其病情自发稳定。神经外表现包括患者1和2的鱼鳞病以及患者1的白内障。这三例病例说明了CONDSIAS临床表现和预后的异质性，突出了主要锥体外系特征和全身受累的发生情况，从而将表型谱扩展到共济失调和癫痫的典型表现之外。
