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α-1-抗胰蛋白酶缺乏症

Alpha-1-antitrypsin deficiency

ORPHA:60疾病中国目录 第2批 · 6

定义 英文原文（暂无中文）

A rare hereditary, metabolic disease characterized by serum levels of alpha-1-antitrypsin (AAT) that are well below the normal range. In the most severe form, the disease can clinically manifest with chronic liver disorders (cirrhosis, fibrosis), respiratory disorders (emphysema, bronchiectasis), and rarely panniculitis or vasculitis.

别名

Alpha-1-proteinase inhibitor deficiency、Alpha1-antitrypsin deficiency

基本事实

遗传方式
常染色体隐性
发病年龄
各年龄段
患病率
1-5 / 10 000（Ireland）

相关基因 1

基因名称关联类型
SERPINA1serpin family A member 1Disease-causing germline mutation(s) in

临床表型 21

极常见 99–80%3

  • 支气管扩张 HP:0002110
  • 气肿 HP:0002097
  • 循环α-1-抗胰蛋白酶水平降低 HP:0032025

常见 79–30%9

  • 支气管炎 HP:0012387
  • 一氧化碳弥散量减少 HP:0045051
  • 循环肝转氨酶水平升高 HP:0002910
  • 肝纤维化 HP:0001395
  • 肝炎 HP:0012115
  • 肝内包涵体 HP:6000976
  • 黄疸 HP:0000952
  • 新生儿高非结合胆红素血症 HP:0008176
  • 新生儿黄疸期延长 HP:0006579

偶见 29–5%7

  • 哮喘 HP:0002099
  • 胆汁淤积 HP:0001396
  • 慢性阻塞性肺疾病 HP:0006510
  • 肝硬化 HP:0001394
  • 细胞质抗中性粒细胞抗体阳性 HP:0032230
  • 婴儿期生长障碍 HP:0001531
  • 门脉高压 HP:0001409

罕见 <4–1%2

  • 肝细胞癌 HP:0001402
  • 脂膜炎 HP:0012490

近两年的全球研究 1,159L2

2024/08 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。

  • 2026-08
    p62/SQSTM1-KEAP1 complex prevents clearance of ubiquitinated Z alpha-1 antitrypsin and aggravates liver proteotoxicity
    The Journal of biological chemistry · DOI · Europe PMC
  • 2026-07
    Emphysema in an 11-month-old boy with alpha-1 antitrypsin deficiency
    Pediatric investigation · DOI · Europe PMC
  • 2026-07
    From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases
    Clinics and research in hepatology and gastroenterology · DOI · Europe PMC
  • 2026-07
    Characterization of US patients with alpha-1 antitrypsin deficiency treated with an alpha-1 proteinase inhibitor
    Journal of medical economics · DOI · Europe PMC
  • 2026-07综述
    Base editing for precision therapeutics
    Cell genomics · DOI · Europe PMC
  • 2026-07
    Evaluating Alpha-1 Antitrypsin Deficiency testing across Europe to ensure diagnostic accuracy: an EARCO multicentre project
    Respiratory research · DOI · Europe PMC
  • 2026-07
    Pizza versus Pi*ZZ: The metabolic amplifiers in alpha-1 antitrypsin deficiency
    Hepatology (Baltimore, Md.) · DOI · Europe PMC
  • 2026-07
    Coexistence of Multiple Endocrine Neoplasia Type 2B and Centri-Acinar Emphysema With Alpha-1 Antitrypsin Deficiency: A Case Report
    Respirology case reports · DOI · Europe PMC
  • 2026-07荟萃分析系统综述综述
    Meta-Analysis: Redefining Liver Disease Risk in Heterozygous Alpha-1 Antitrypsin Deficiency
    Alimentary pharmacology & therapeutics · DOI · Europe PMC
  • 2026-07
    Community-Based &lt;i&gt;SERPINA1&lt;/i&gt; Genotyping in an Isolated Alpine Town Reveals Heterozygous Pi*Mheerlen Carriers: Implications for Targeted Screening
    Biomedicines · DOI · Europe PMC
  • 2026-07
    Delineating a reference interval for functional alpha-1 antitrypsin in the serum of healthy Pi*MM donors using an anti-neutrophil elastase capacity assay
    Respiratory research · DOI · Europe PMC
  • 2026-07
    Gene Therapy: Knowledge, Attitudes, and Preferences Among Individuals with Alpha-1 Antitrypsin Deficiency
    Chronic obstructive pulmonary diseases (Miami, Fla.) · DOI · Europe PMC
  • 2026-06
    Dissociation of the Hepatic and Pulmonary Axes in Alpha-1 Antitrypsin Deficiency: Independent Trajectories of Organ-Specific Disease
    Biomolecules · DOI · Europe PMC
  • 2026-06开放获取
    An Explainable AI Framework for Continuous Monitoring, Risk Stratification, and Clinical Decision Support in Primary Biliary Cholangitis: Protocol for a Multiphase Development and Validation Study
    JMIR research protocols · DOI · Europe PMC
  • 2026-06病例报告
    Hepatic Alpha-1 Antitrypsin Globules in Compound Heterozygous SERPINA1 Variants Previously Considered Non-Polymerizing: A Case Report
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-06开放获取
    Retraction: The Irish National Alpha-1 Antitrypsin Deficiency (AATD) Registry: Examining the Prevalence of Radiological Abnormalities in a Population With Severe AATD
    Cureus · DOI · Europe PMC
  • 2026-06开放获取
    Ultrasonographic and serum biomarkers for diagnosis of biliary atresia
    Pediatric surgery international · DOI · Europe PMC
  • 2026-06
    Spanish Clinical Practice Guidelines for the Diagnosis and Management of Alpha-1 Antitrypsin Deficiency: 2026 Update
    Archivos de bronconeumologia · DOI · Europe PMC
  • 2026-06
    Biophysical and Computational Insights into Alpha-1 Antitrypsin Aggregation and Its Inhibition by Natural Polyphenols
    Biomedicines · DOI · Europe PMC
  • 2026-06综述开放获取
    Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles
    Materials today. Bio · DOI · Europe PMC

境外已获批用于本病的药物 0L2

欧盟与美国均未检索到已获批用于本病的药物。

已获孤儿药资格、尚未获批的在研药物（24 项）

孤儿药资格只是一种监管身份——它意味着监管机构认可这是罕见病用药并给予研发激励，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。

  • human alpha1-proteinase inhibitor欧盟2001-07-09
    Treatment of emphysema secondary to congenital alpha-1 antitrypsin deficiency
    官方记录
  • Infinia欧盟2004-11-16
    alpha-1 antitrypsin
    Treatment of emphysema secondary to congenital alpha-1 antitrypsin deficiency
    官方记录
  • recombinant adeno-associated viral vector containing human alpha-1 ant欧盟2007-03-20
    Treatment of congenital alpha-1 antitrypsin deficiency
    官方记录
  • Cyclo[L-alanyl-L-seryl-L-isoleucyl-L-prolyl-L-prolyl-L-glutaminyl-L-ly欧盟2013-03-20
    Treatment of congenital alpha-1 antitrypsin deficiency
    官方记录
  • N-acetylgalactosamine-conjugated synthetic double-stranded oligomer sp欧盟2018-07-31
    Treatment of congenital alpha-1 antitrypsin deficiency
    官方记录
  • N-[(1R)-1-[(S)-(2-Chloro-3-fluorophenyl)hydroxymethyl]butyl]-7-fluoro-欧盟2024-07-25
    Treatment of congenital alpha-1 antitrypsin deficiency
    官方记录
  • alvelestat欧盟2025-01-16
    Treatment of congenital alpha-1 antitrypsin deficiency
    官方记录
  • efdoralprin alfa欧盟2025-12-09
    Treatment of alpha-1 antitrypsin deficiency
    官方记录
  • Transgenic human alpha 1 antitrypsin美国1999-05-19
    Treatment of emphysema secondary to alpha 1 antitrypsin deficiency.
    官方记录
  • hyaluronic acid美国2002-03-19
    Treatment of emphysema in patients due to alpha-1 antitrypsin deficiency
    官方记录
  • recombinant adeno-associated virus alpha 1-antitrypsin vector美国2003-01-27
    Treatment of alpha1-antitrypsin deficiency
    官方记录
  • alpha1 proteinase inhibitor (human)美国2010-01-29
    Treatment of emphysema secondary to congenital alpha1-antitrypsin deficiency.
    官方记录
  • double stranded oligomer ADS-001 RNA interference-based liver targeted美国2018-02-14
    Treatment of alpha-1 antitrypsin deficiency
    官方记录
  • Recombinant human alpha-1 antitrypsin from Oryza sativa美国2020-02-19
    Treatment of alpha-1 antitrypsin deficiency
    官方记录
  • CHO cell line produced human Alpha-1 Antitrypsin (CHO-AAT) protein美国2020-10-19
    treatment of alpha-1 antitrypsin deficiency
    官方记录
  • Alvelestat美国2021-10-25
    Treatment of Alpha-1 Antitrypsin Deficiency
    官方记录
  • IgG4 Fc linked recombinant human AAT (alpha-1 antitrypsin)美国2022-03-02
    Treatment of Congenital Alpha-1 Antitrypsin Deficiency (AATD)
    官方记录
  • A replication-defective, non-integrating herpes simplex virus type 1-b美国2023-09-01
    Treatment of Alpha-1 antitrypsin deficiency
    官方记录
  • oxoindoline carboxamide compound美国2023-12-12
    Treatment of alpha-1 antitrypsin deficiency
    官方记录
  • RNA editing antisense oligonucleotide (ASO) KB100967 directed at the Z美国2025-03-12
    treatment of alpha-1 antitrypsin deficiency (AATD)
    官方记录
  • lipid nanoparticles containing base editor CRISPR-Cas9 messenger RNA (美国2025-04-09
    treatment of alpha-1 antitrypsin deficiency
    官方记录
  • a lipid nanoparticle-based therapy consisting of a guide RNA that targ美国2025-05-28
    treatment of alpha-1 antitrypsin deficiency
    官方记录
  • in vivo target-primed reverse transcription genome editing product con美国2025-11-06
    treatment of alpha-1 antitrypsin deficiency (AATD)
    官方记录
  • RNA editing antisense oligonucleotide (ASO)美国2025-11-19
    treatment of alpha-1 antitrypsin deficiency.”
    官方记录

数据来自欧洲药品管理局（EMA）的药品与孤儿药资格公开导出表，以及美国 FDA 孤儿药资格数据库。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 1L2

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。

当前没有检索到登记为可入组的试验。

其他状态的试验（1 项）
  • 进行中·不再招募NCT07193615
    Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
    早期 I 期 · 干预性 · 2025/06/18RenJi Hospital
    中国研究中心 1 个：Shanghai

中国境外的在招试验 24L2

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14英国6德国4爱尔兰4西班牙4澳大利亚4法国4丹麦3荷兰3波兰3葡萄牙3瑞典3奥地利3比利时2另有 9 个国家/地区

共 24 项。

  • 尚未开始招募NCT07639996
    Natural Course and Molecular Basis of Alpha 1- Antitrypsin Deficiency-associated Liver Disease.
    观察性 · 2026/10/01Assiut University
  • 尚未开始招募NCT07326592
    Phase 4, Double-blind Study Evaluating the Response on Computed Tomography (CT) Lung Density Decline Rates of Respreeza / Zemaira Weekly for 3 Years in Adults With alpha1 Antitrypsin Deficiency (AATD)
    IV 期 · 干预性 · 2026/07/20CSL Behring
  • 尚未开始招募NCT07707635
    IBS-Oriented CDED Versus Low FODMAP Diet for Irritable Bowel Syndrome
    不适用 · 干预性 · 2026/07/07Ariel University
  • 招募中NCT07555483
    A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD)
    III 期 · 干预性 · 2026/05/05Grifols Therapeutics LLC
    丹麦、德国、爱尔兰、荷兰、波兰、葡萄牙、西班牙、瑞典 等 9 国
  • 招募中NCT07227207
    A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)
    I 期、II 期 · 干预性 · 2026/04/21Tessera Therapeutics, Inc.
    澳大利亚、英国、美国
  • 招募中NCT07431112
    A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD)
    I 期 · 干预性 · 2026/03/17AIRNA Corporation
    澳大利亚、Georgia、英国
  • 招募中NCT07715617
    Development of a Prediction Score for the Occurrence of Death or Lung Transplantation in Patients With Emphysema Secondary to Alpha-1-anti-tripsin Deficiency
    观察性 · 2026/02/16University Hospital, Bordeaux
    法国
  • 尚未开始招募NCT07145385
    Prevalence of Alpha-1 Antitrypsin Deficiency in Non-Cirrhotic Liver Cancer
    观察性 · 2026/01University Hospital, Bordeaux
    法国
  • 招募中NCT07135427
    Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency
    IV 期 · 干预性 · 2025/09/03University of Alabama at Birmingham
    美国
  • 招募中NCT07152834
    Screening for Alpha-1 Antitrypsin Deficiency in Patients With Airway Obstruction
    观察性 · 2025/08/06Muğla Sıtkı Koçman University
    土耳其
  • 招募中NCT06505603
    PiMZ Longitudinal Cohort (PiMZ Logic)
    观察性 · 2025/05/30Columbia University
    美国
  • 招募中NCT06996756
    Gene Therapy for Alpha 1- Antitrypsin Deficiency
    I 期 · 干预性 · 2025/02/26Weill Medical College of Cornell University
    美国
  • 招募中NCT06512454
    A Study in Adults to Learn About Inherited Alpha-1 Antitrypsin Deficiency (AATD) and AATD Related Liver Problems
    观察性 · 2024/09/25Takeda
    奥地利、德国、爱尔兰、西班牙、英国、美国
  • 招募中NCT06389877
    A Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)
    I 期、II 期 · 干预性 · 2024/06/19Beam Therapeutics Inc.
    澳大利亚、爱尔兰、荷兰、新西兰、英国、美国
  • 招募中NCT06165341
    Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis)
    III 期 · 干预性 · 2024/03/01Takeda
    奥地利、比利时、加拿大、法国、德国、意大利、波兰、葡萄牙 等 13 国

外部标识与链接

OrphanetOMIM:613490MONDO:0013282GARD:5784ICD-10 E88.0ICD-11 5C5AClinicalTrials.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）