儿童遗传性共济失调的诊治进展
Advances in Diagnosis and Treatment of Hereditary Ataxias in Children
DOI: 10.12677/acm.2026.161074, PDF,    国家自然科学基金支持
作者: 金璐瑶, 江 伟*：重庆医科大学附属儿童医院康复科，儿童少年健康与疾病国家临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿童神经发育与认知障碍重庆市重点实验室，重庆
关键词: 小脑疾病；遗传；儿童；共济失调；Cerebellar Disorders； Genetic； Children； Ataxia
摘要: 儿童遗传性共济失调是一组具有高度临床和遗传异质性的神经退行性疾病，核心表现为小脑功能障碍及相关神经系统症状。该病包含多种遗传模式(常染色体显/隐性、X连锁及线粒体遗传)，涉及蛋白质稳态失调、RNA毒性等多重致病机制。目前诊断主要依靠基因检测技术，治疗方面除FRDA等少数亚型有获批靶向药物外，多数仍以对症支持为主。本文系统综述了该疾病的诊断策略及治疗新进展。
Abstract: Pediatric hereditary ataxias represent a group of neurodegenerative disorders characterized by high clinical and genetic heterogeneity, with core manifestations of cerebellar dysfunction and associated neurological symptoms. These diseases encompass diverse inheritance patterns (autosomal dominant/recessive, X-linked, and mitochondrial) and involve multiple pathogenic mechanisms, including protein homeostasis dysregulation and RNA toxicity. Current diagnosis primarily relies on genetic testing, while treatment remains largely supportive, except for a few subtypes such as FRDA that have approved targeted therapies. This review systematically summarizes the molecular mechanisms, diagnostic strategies, and recent therapeutic advances in this field.
文章引用：金璐瑶, 江伟. 儿童遗传性共济失调的诊治进展[J]. 临床医学进展, 2026, 16(1): 546-553. https://doi.org/10.12677/acm.2026.161074

参考文献

[1] Ataullah, A.H.M., Singla, R. and Naqvi, I.A. (2024) Cerebellar Dysfunction. StatPearls.
[2] Schmahmann, J.D. (2019) The Cerebellum and Cognition. Neuroscience Letters, 688, 62-75. [Google Scholar] [CrossRef] [PubMed]
[3] Németh, A.H., Kwasniewska, A.C., Lise, S., Parolin Schnekenberg, R., Becker, E.B.E., Bera, K.D., et al. (2013) Next Generation Sequencing for Molecular Diagnosis of Neurological Disorders Using Ataxias as a Model. Brain, 136, 3106-3118. [Google Scholar] [CrossRef] [PubMed]
[4] Renaud, M., Tranchant, C., Martin, J.V.T., Mochel, F., Synofzik, M., van de Warrenburg, B., et al. (2017) A Recessive Ataxia Diagnosis Algorithm for the Next Generation Sequencing Era. Annals of Neurology, 82, 892-899. [Google Scholar] [CrossRef] [PubMed]
[5] Arslan, E.A., Göçmen, R., Oğuz, K.K., Konuşkan, G.D., Serdaroğlu, E., Topaloğlu, H., et al. (2017) Childhood Hereditary Ataxias: Experience from a Tertiary Referral University Hospital in Turkey. Acta Neurologica Belgica, 117, 857-865. [Google Scholar] [CrossRef] [PubMed]
[6] Perucca, G., Leboucq, N., Roubertie, A., Rivier, F., Menjot, N., Valentini, C., et al. (2016) Role of Neuroimaging in the Diagnosis of Hereditary Cerebellar Ataxias in Childhood. Journal of Neuroradiology, 43, 176-185. [Google Scholar] [CrossRef] [PubMed]
[7] Pagani, E., Ginestroni, A., Della Nave, R., Agosta, F., Salvi, F., De Michele, G., et al. (2010) Assessment of Brain White Matter Fiber Bundle Atrophy in Patients with Friedreich Ataxia. Radiology, 255, 882-889. [Google Scholar] [CrossRef] [PubMed]
[8] Pyle, A., Smertenko, T., Bargiela, D., Griffin, H., Duff, J., Appleton, M., et al. (2014) Exome Sequencing in Undiagnosed Inherited and Sporadic Ataxias. Brain, 138, 276-283. [Google Scholar] [CrossRef] [PubMed]
[9] Traschütz, A., Reich, S., Adarmes, A.D., Anheim, M., Ashrafi, M.R., Baets, J., et al. (2021) The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias. Frontiers in Neurology, 12, Article 677551. [Google Scholar] [CrossRef] [PubMed]
[10] Bogdanova-Mihaylova, P., Hebert, J., Moran, S., Murphy, M., Ward, D., Walsh, R.A., et al. (2020) Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic. The Cerebellum, 20, 54-61. [Google Scholar] [CrossRef] [PubMed]
[11] Coutelier, M., Hammer, M.B., Stevanin, G., Monin, M., Davoine, C., Mochel, F., et al. (2018) Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes. JAMA Neurology, 75, 591-599. [Google Scholar] [CrossRef] [PubMed]
[12] Fogel, B.L., Lee, H., Deignan, J.L., Strom, S.P., Kantarci, S., Wang, X., et al. (2014) Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia. JAMA Neurology, 71, 1237-1246. [Google Scholar] [CrossRef] [PubMed]
[13] Lynch, D.R., Chin, M.P., Boesch, S., Delatycki, M.B., Giunti, P., Goldsberry, A., et al. (2022) Efficacy of Omaveloxolone in Friedreich’s Ataxia: Delayed‐Start Analysis of the Moxie Extension. Movement Disorders, 38, 313-320. [Google Scholar] [CrossRef] [PubMed]
[14] Kang, L., Jin, S., Wang, J., Lv, Z., Xin, C., Tan, C., et al. (2023) AAV Vectors Applied to the Treatment of CNS Disorders: Clinical Status and Challenges. Journal of Controlled Release, 355, 458-473. [Google Scholar] [CrossRef] [PubMed]
[15] (2025) Lexeo Therapeutics Announces Positive Interim Phase 1/2 Clinical Data of LX2006 for the Treatment of Friedreich Ataxia Cardiomyopathy. Lexeo Therapeutics.
https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-phase-12-clinical
[16] (2020) High-Dose AAV Gene Therapy Deaths. Nature Biotechnology, 38, 910.
[17] Li, C. and Samulski, R.J. (2020) Engineering Adeno-Associated Virus Vectors for Gene Therapy. Nature Reviews Genetics, 21, 255-272. [Google Scholar] [CrossRef] [PubMed]
[18] Gonzalez, T.J., Mitchell-Dick, A., Blondel, L.O., Fanous, M.M., Hull, J.A., Oh, D.K., et al. (2023) Structure-Guided AAV Capsid Evolution Strategies for Enhanced CNS Gene Delivery. Nature Protocols, 18, 3413-3459. [Google Scholar] [CrossRef] [PubMed]
[19] Wang, J., Gessler, D.J., Zhan, W., Gallagher, T.L. and Gao, G. (2024) Adeno-Associated Virus as a Delivery Vector for Gene Therapy of Human Diseases. Signal Transduction and Targeted Therapy, 9, Article No. 78. [Google Scholar] [CrossRef] [PubMed]
[20] Britti, E., Delaspre, F., Feldman, A., Osborne, M., Greif, H., Tamarit, J., et al. (2017) Frataxin‐Deficient Neurons and Mice Models of Friedreich Ataxia Are Improved by TAT‐MTScs‐FXN Treatment. Journal of Cellular and Molecular Medicine, 22, 834-848. [Google Scholar] [CrossRef] [PubMed]
[21] Scoles, D.R., Meera, P., Schneider, M.D., Paul, S., Dansithong, W., Figueroa, K.P., et al. (2017) Antisense Oligonucleotide Therapy for Spinocerebellar Ataxia Type 2. Nature, 544, 362-366. [Google Scholar] [CrossRef] [PubMed]
[22] Zu, T., Guo, S., Bardhi, O., Ryskamp, D.A., Li, J., Khoramian Tusi, S., et al. (2020) Metformin Inhibits RAN Translation through PKR Pathway and Mitigates Disease in C9orf72 ALS/FTD Mice. Proceedings of the National Academy of Sciences of the United States of America, 117, 18591-18599. [Google Scholar] [CrossRef] [PubMed]
[23] Nguyen, L., Montrasio, F., Pattamatta, A., Tusi, S.K., Bardhi, O., Meyer, K.D., et al. (2020) Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model. Neuron, 105, 645-662.e11. [Google Scholar] [CrossRef] [PubMed]
[24] Urrutia, J., Arrizabalaga-Iriondo, A., Sanchez-del-Rey, A., Martinez-Ibargüen, A., Gallego, M., Casis, O., et al. (2024) Therapeutic Role of Voltage-Gated Potassium Channels in Age-Related Neurodegenerative Diseases. Frontiers in Cellular Neuroscience, 18, Article 1406709. [Google Scholar] [CrossRef] [PubMed]
[25] Yang, B., Dan, X., Hou, Y., Lee, J., Wechter, N., Krishnamurthy, S., et al. (2021) NAD+ Supplementation Prevents Sting‐Induced Senescence in Ataxia Telangiectasia by Improving Mitophagy. Aging Cell, 20, e13329. [Google Scholar] [CrossRef] [PubMed]
[26] Finno, C.J., Peterson, J., Kang, M., Park, S., Bordbari, M.H., Durbin-Johnson, B., et al. (2019) Single-Cell RNA-Seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency. iScience, 21, 720-735. [Google Scholar] [CrossRef] [PubMed]
[27] Boasinha, A.S., Murtinheira, F., Solá, S., Gomes, C.M. and Herrera, F. (2025) S100B Mitigates Cytoskeletal and Mitochondrial Alterations in a Glial Cell Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. Molecular Neurobiology, 62, 12296-12306. [Google Scholar] [CrossRef] [PubMed]

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