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Leber先天性黑矇

Leber congenital amaurosis

ORPHA:65疾病中国目录 第2批 · 43

定义 英文原文（暂无中文）

Leber congenital amaurosis (LCA) is a retinal dystrophy defined by blindness and responses to electrophysiological stimulation (Ganzfeld electroretinogram (ERG)) below threshold, associated with severe visual impairment within the first year of life.

别名

Leber先天性黒矇

基本事实

遗传方式
常染色体显性、常染色体隐性
发病年龄
婴儿期、新生儿期
患病率
1-9 / 100 000（Europe）

相关基因 26

基因名称关联类型
PRPH2peripherin 2Disease-causing germline mutation(s) in
RD3RD3 regulator of GUCY2DDisease-causing germline mutation(s) in
RDH12retinol dehydrogenase 12Disease-causing germline mutation(s) (loss of function) in
RPE65retinoid isomerohydrolase RPE65Disease-causing germline mutation(s) in
RPGRIP1RPGR interacting protein 1Disease-causing germline mutation(s) (loss of function) in
CABP4calcium binding protein 4Disease-causing germline mutation(s) in
CEP290centrosomal protein 290Disease-causing germline mutation(s) in
AIPL1AIP like 1 HSP90 co-chaperoneDisease-causing germline mutation(s) in
ALMS1ALMS1 centrosome and basal body associated proteinDisease-causing germline mutation(s) in
TULP1TUB like protein 1Disease-causing germline mutation(s) in
CRB1crumbs cell polarity complex component 1Disease-causing germline mutation(s) in
CRXcone-rod homeoboxDisease-causing germline mutation(s) in
GUCY2Dguanylate cyclase 2D, retinalDisease-causing germline mutation(s) (loss of function) in
IMPDH1inosine monophosphate dehydrogenase 1Disease-causing germline mutation(s) in
IQCB1IQ motif containing B1Disease-causing germline mutation(s) (loss of function) in
OTX2orthodenticle homeobox 2Disease-causing germline mutation(s) in
LCA5lebercilin LCA5Disease-causing germline mutation(s) in
KCNJ13potassium inwardly rectifying channel subfamily J member 13Disease-causing germline mutation(s) in
LRATlecithin retinol acyltransferaseDisease-causing germline mutation(s) in
SPATA7spermatogenesis associated 7Disease-causing germline mutation(s) in
GDF6growth differentiation factor 6Disease-causing germline mutation(s) in
IFT140intraflagellar transport 140Disease-causing germline mutation(s) in
NMNAT1nicotinamide nucleotide adenylyltransferase 1Disease-causing germline mutation(s) in
PCYT1Aphosphate cytidylyltransferase 1A, cholineDisease-causing germline mutation(s) (loss of function) in
USP45ubiquitin specific peptidase 45Disease-causing germline mutation(s) in
TUBB4Btubulin beta 4B class IVbDisease-causing germline mutation(s) in

临床表型 25

极常见 99–80%3

  • 视网膜色素异常 HP:0007703
  • 视盘形态异常 HP:0012795
  • 视力严重下降 HP:0001141

常见 79–30%15

  • 视网膜电图异常 HP:0000512
  • 全视野视网膜电图异常 HP:0030466
  • 神经细胞迁移异常 HP:0002269
  • 小脑蚓部发育缺陷/发育不全 HP:0006817
  • 白内障 HP:0000518
  • 脑膨出 HP:0002084
  • 戳眼 HP:0001483
  • 偏瘫/轻偏瘫 HP:0004374
  • 远视 HP:0000540
  • 肌张力减退 HP:0001252
  • 圆锥角膜 HP:0000563
  • 眼球震颤 HP:0000639
  • 畏光 HP:0000613
  • 癫痫发作 HP:0001250
  • 瞳孔对光反应缓慢 HP:0030211

偶见 29–5%7

  • 自闭症行为 HP:0000729
  • 全面发育迟缓 HP:0001263
  • 听力受损 HP:0000365
  • 智力障碍 HP:0001249
  • 运动发育迟缓 HP:0001270
  • 视盘玻璃疣 HP:0012426
  • 视盘苍白 HP:0000543

近两年的全球研究 891L2

2024/10 起在 Europe PMC 检索所得，按发表时间倒序显示最近 20 篇。标题未译成中文——自动翻译需要接入 LLM 服务，尚未引入。

  • 2026-10开放获取
    Small populations, big impact: leveraging rare disease gene therapies to benefit millions
    The Journal of clinical investigation · DOI · Europe PMC
  • 2026-09综述开放获取
    Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives
    Pharmaceutics · DOI · Europe PMC
  • 2026-09综述开放获取
    Comorbid Auditory and Visual Dysfunction: From Pathogenic Genes to Gene Therapy
    Genes · DOI · Europe PMC
  • 2026-09开放获取
    A comprehensive overview of genetic mutations in Iranian patients with Bardet-Biedl syndrome
    Molecular genetics and metabolism reports · DOI · Europe PMC
  • 2026-09开放获取
    Early Molecular Testing for Presumptive Genetic Eye Diseases
    Genes · DOI · Europe PMC
  • 2026-09开放获取
    A national cross-sectional study of patients with inherited retinal disease in China
    Scientific reports · DOI · Europe PMC
  • 2026-09开放获取
    Dynamic pupillometry in patients with visible optic disc drusen: a cross-sectional study
    BMC ophthalmology · DOI · Europe PMC
  • 2026-09
    Clinical and Population-Specific Insights Into Inherited Retinal Dystrophies From Whole-Exome Sequencing of the Polish Cohort
    Investigative ophthalmology & visual science · DOI · Europe PMC
  • 2026-09综述开放获取
    CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases
    Clinical and translational medicine · DOI · Europe PMC
  • 2026-08荟萃分析系统综述开放获取
    Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis
    Angiogenesis · DOI · Europe PMC
  • 2026-08综述开放获取
    Advances in gene transfer technologies: comparing viral and non-viral vectors for therapeutic applications
    3 Biotech · DOI · Europe PMC
  • 2026-08开放获取
    Association of <i>ABHD12</i> Variants with the Spectrum of PHARC Syndrome Phenotypes
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-08综述开放获取
    Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials
    Journal of clinical medicine · DOI · Europe PMC
  • 2026-08综述开放获取
    Nicotinamide Mononucleotide Adenylyltransferase 1 and NAD<sup>+</sup> Homeostasis in Neuroprotection and Aging
    Metabolites · DOI · Europe PMC
  • 2026-08综述开放获取
    Integration of CCT/TRiC assembly, degradation and function: Chaperonin complexity in a cellular context
    Cell stress & chaperones · DOI · Europe PMC
  • 2026-08
    CLUAP1 variants cause non-syndromic retinitis pigmentosa
    Graefe's archive for clinical and experimental ophthalmology = Albrech · DOI · Europe PMC
  • 2026-08开放获取
    Dissecting Missing Heritability in Rare Inherited Macular Dystrophies
    Genes · DOI · Europe PMC
  • 2026-08
    Aetiology, characteristics and workup of early onset high myopia
    The British journal of ophthalmology · DOI · Europe PMC
  • 2026-08开放获取
    Ability of Large Language Models to Answer Patients' Questions and Generate Educational Materials for Uncommon Retinal Conditions
    Journal of vitreoretinal diseases · DOI · Europe PMC
  • 2026-08开放获取
    A text mining and ontology-based approach using phenotypes to obtain relevant literature for rare diseases
    iScience · DOI · Europe PMC

境外已获批用于本病的药物 1L2

欧盟 1 项、美国 0 项。同一药物在两地各批一次的，会分别列出。

「境外已获批」不等于「在中国能用」。中间隔着进口注册、临床急需境外新药通道、海南博鳌乐城国际医疗旅游先行区等几条路径，各有各的条件与费用。这一节能确定地告诉你的只有一件事：这个病在世界范围内已经有获得批准的药物，它叫什么名字。拿这个名字去问主治医生，是下一步最省力的做法。

药名一律保留英文原文，不作翻译——中国的药品通用名与英文名的音译经常不一致，译错会让人去找一个不存在的药。

尚未获批的在研药物（5 项）

这些药已被欧盟或美国的监管机构认定为罕见病用药（英文 orphan drug designation，中文行业里通称「孤儿药资格」——「孤儿」说的是这类药市场太小、没有厂商愿意认领，不是在说病人）。但这只是一种监管身份：意味着监管机构给予研发上的激励，不代表这个药已被证明有效，也不代表将来一定能上市，绝大多数最终不会成药。列在这里是为了看清有哪些方向正在被尝试。

  • Recombinant adeno-associated virus retinal pigment epithelium gene vec美国2008-06-24
    Treatment of Leber congenital amaurosis due to RPE65 mutations.
    官方记录
  • adenovirus associated viral vector serotype 5 containing the human RPE美国2016-03-10
    Treatment of Leber congenital amaurosis
    官方记录
  • adenovirus associated viral vector serotype 8 containing the human AIP美国2018-02-01
    Treatment of inherited retinal dystrophy due to defects in AIPL1 gene, including Leber congenital amaurosis, retinitis pigmentosa, and cone-rod dystrophy
    官方记录
  • Human Nuclear Hormone Receptor Subfamily 2 Group E Member 3 (hNR2E3)美国2022-12-15
    Treatment of Leber congenital amaurosis
    官方记录
  • adeno-associated virus serotype 8 vector containing single-stranded DN美国2024-09-18
    treatment of retinal dystrophy due to mutations in the lebercilin gene, including Leber congenital amaurosis
    官方记录

数据来自欧洲药品管理局（EMA）的药品与罕见病用药资格公开导出表，以及美国 FDA 的罕见病用药资格数据库（Orphan Drug Product Designation Database）。两边口径不同：欧盟一侧取的是当前状态仍为「已授权」的药品；美国一侧记录的是「曾获批准」这一事实，FDA 的公开表不追踪药物此后是否退市（例如 Relyvrio 于 2024 年撤市，表中仍记为已获批）。请以官方记录页为准。

在中国开展的临床试验 3L2

按病名在 ClinicalTrials.gov 检索、并校验研究中心含中国大陆而来。登记状态不等于现在真的能入组——务必按 NCT 号到原站核实，并与主治医生商量。

登记为可入组 1

  • 招募中NCT05906953
    Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
    I 期、II 期 · 干预性 · 2023/10/31HuidaGene Therapeutics Co., Ltd.
    中国研究中心 1 个：Shanghai
其他状态的试验（2 项）
  • 状态未知NCT03566147
    Treatment of RP and LCA by Primary RPE Transplantation
    早期 I 期 · 干预性 · 2018/08/01Eyecure Therapeutics Inc.
    中国研究中心 1 个：Beijing
  • 进行中·不再招募NCT06088992
    Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
    早期 I 期 · 干预性 · 2023/01/10Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
    中国研究中心 1 个：Shanghai

中国境外的在招试验 6L2

这些试验在中国没有研究中心，通常无法直接报名——入组一般要求在当地居住并接受随访。列在这里是因为它另有用处：看清楚全世界正在试哪些药、做到了哪一期、由谁在做。把药名和 NCT 编号记下来去问主治医生，或据此进一步查该药是否已在境外获批、是否有拓展性用药（expanded access）通道。

美国4比利时1巴西1加拿大1法国1德国1荷兰1西班牙1英国1澳大利亚1

CT.gov 报告命中 6 项，此处取回并展示最近的 5 项。

  • 尚未开始招募NCT07681778
    Safety and Tolerability of Subretinal OPGx-RDH12-1001 for LCA-Associated Inherited Retinal Degeneration (LCA-IRD)
    I 期、II 期 · 干预性 · 2026/09/01Opus Genetics, Inc
    美国
  • 招募中NCT06891443
    Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
    III 期 · 干预性 · 2025/06/04Laboratoires Thea
    比利时、巴西、加拿大、法国、德国、荷兰、西班牙、英国 等 9 国
  • 尚未开始招募NCT06024057
    An Expanded Clinical Study Evaluating the AAV2-RPE65 Gene Therapy(LX101) in Patients With LCA
    不适用 · 干预性 · 2023/09/01Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
  • 招募中NCT02435940
    Inherited Retinal Degenerative Disease Registry
    观察性 · 2014/06Foundation Fighting Blindness
    美国
  • 招募中NCT01793168
    Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
    观察性 · 2010/07Sanford Health
    澳大利亚、美国

外部标识与链接

OrphanetOMIM:179900OMIM:204000OMIM:204100MONDO:0018998GARD:634ICD-10 H35.5ICD-11 9B70ClinicalTrials.gov 检索

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本页数据来源

  • 疾病定义、同义词、基因、表型、流行病学：Orphanet（CC BY 4.0）
  • 中文病名：Orphanet 中文包，冻结于 2020-06-01
  • 表型中文标签：HPO 简体中文翻译（CHPO 上游成果）