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遗传性痉挛性截瘫

Hereditary spastic paraplegia

ORPHA:685疾病组中国目录 第1批 · 43

定义 英文原文（暂无中文）

A genetically and clinically heterogeneous group of slowly progressive neurological disorders which in the pure form is characterized by pyramidal signs (weakness, spasticity, brisk tendon reflexes, and extensor plantar responses) predominantly affecting the lower limbs and with possible association of sphincter disturbances and deep sensory loss; and in the complex form by the addition of variable neurological or non-neurological features.

别名

遗传性痉挛性下肢轻瘫

基本事实

遗传方式
常染色体显性、常染色体隐性、X 连锁隐性
发病年龄
各年龄段
患病率
1-9 / 100 000（Europe）

相关基因 60来自下位疾病

Orphanet 未在本条目上直接标注致病基因。下表由本组所属的下位疾病汇总而来，「来源条目」列给出基因实际标注在哪一个 ORPHA 条目上。

基因名称来源条目
ALDH18A1aldehyde dehydrogenase 18 family member A1ORPHA:447760
AMPD2adenosine monophosphate deaminase 2ORPHA:401805
AP5Z1adaptor related protein complex 5 subunit zeta 1ORPHA:306511
ARL6IP1ARL6 interacting reticulophagy regulator 1ORPHA:401780
ARSIarylsulfatase family member IORPHA:401815
ATP13A2ATPase cation transporting 13A2ORPHA:513436
B4GALNT1beta-1,4-N-acetyl-galactosaminyltransferase 1ORPHA:101006
BSCL2BSCL2 lipid droplet biogenesis associated, seipinORPHA:100998
C19ORF12chromosome 19 open reading frame 12ORPHA:320370
CAPN1calpain 1ORPHA:488594
CCT5chaperonin containing TCP1 subunit 5ORPHA:139578
CPT1Ccarnitine palmitoyltransferase 1CORPHA:444099
CYP2U1cytochrome P450 family 2 subfamily U member 1ORPHA:320411
CYP7B1cytochrome P450 family 7 subfamily B member 1ORPHA:100986
DDHD1DDHD domain containing 1ORPHA:101008
DDHD2DDHD domain containing 2ORPHA:320380
DSTYKdual serine/threonine and tyrosine protein kinaseORPHA:101003
ENTPD1ectonucleoside triphosphate diphosphohydrolase 1ORPHA:401810
ERLIN1ER lipid raft associated 1ORPHA:401785
ERLIN2ER lipid raft associated 2ORPHA:209951
FA2Hfatty acid 2-hydroxylaseORPHA:171629
FARS2phenylalanyl-tRNA synthetase 2, mitochondrialORPHA:466722
FLRT1fibronectin leucine rich transmembrane protein 1ORPHA:320406
GBA2glucosylceramidase beta 2ORPHA:320391
GJC2gap junction protein gamma 2ORPHA:320401
GPT2glutamic--pyruvic transaminase 2ORPHA:477673
HACE1HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1ORPHA:464282
HPDL4-hydroxyphenylpyruvate dioxygenase likeORPHA:631076
HSPD1heat shock protein family D (Hsp60) member 1ORPHA:100994
IBA57iron-sulfur cluster assembly factor IBA57ORPHA:468661
KIDINS220kinase D interacting substrate 220ORPHA:521390
KIF1Akinesin family member 1AORPHA:101010
KIF1Ckinesin family member 1CORPHA:397946
KIF5Akinesin family member 5AORPHA:100991
KLC2kinesin light chain 2ORPHA:320406
KPNA3karyopherin subunit alpha 3ORPHA:171612
KYkyphoscoliosis peptidaseORPHA:496689
L1CAML1 cell adhesion moleculeORPHA:2466
MAGmyelin associated glycoproteinORPHA:459056
MARS1methionyl-tRNA synthetase 1ORPHA:401835
MFN2mitofusin 2ORPHA:64751
MT-ATP6mitochondrially encoded ATP synthase membrane subunit 6ORPHA:320360
MTRFRmitochondrial translation release factor in rescueORPHA:320375
NIPA1NIPA magnesium transporter 1ORPHA:100988
NT5C25'-nucleotidase, cytosolic IIORPHA:320396
PCYT2phosphate cytidylyltransferase 2, ethanolamineORPHA:631073
PGAP1post-GPI attachment to proteins inositol deacylase 1ORPHA:401820
PLP1proteolipid protein 1ORPHA:99015
PNPLA6patatin like domain 6, lysophospholipaseORPHA:139480
RAB3GAP2RAB3 GTPase activating non-catalytic protein subunit 2ORPHA:401830
REEP1receptor accessory protein 1ORPHA:101011
REEP2receptor accessory protein 2ORPHA:401849
RTN2reticulon 2ORPHA:100993
SELENOIselenoprotein IORPHA:506353
SLC33A1solute carrier family 33 member 1ORPHA:171863
SPARTspartinORPHA:101000
SPASTspastinORPHA:100985
SPG11SPG11 vesicle trafficking associated, spatacsinORPHA:2822
SPG14spastic paraplegia 14 (autosomal recessive)ORPHA:100995
SPG16spastic paraplegia 16 (complicated, X-linked recessive)ORPHA:100997

近两年的全球研究 975L2

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
    A De Novo ATP1A3 p.Arg995His Variant in a Patient With an Adult-Onset Primary Lateral Sclerosis-Like Syndrome
    Clinical genetics · DOI · Europe PMC
  • 2026-10病例报告
    Hereditary Spastic Paraplegia Type 11: A Comprehensive Case Report
    Mymensingh medical journal : MMJ · Europe PMC
  • 2026-09综述
    Hereditary spastic paraplegia: a practical approach
    Practical neurology · DOI · Europe PMC
  • 2026-09
    Serine palmitoyltransferase (SPT) inhibition in SPTSSA-related complex hereditary spastic paraplegia
    JCI insight · DOI · Europe PMC
  • 2026-09开放获取
    Subtle hypometabolism on [<sup>18</sup>F]FDG-PET, yet absent [<sup>123</sup>I]FP-CIT SPECT binding in a patient with spastic paraplegia type 7
    EJNMMI reports · DOI · Europe PMC
  • 2026-09开放获取
    Hereditary and Non-hereditary Cerebellar Ataxias in Latvia: Six Years of Experience at the National Reference Centre (ERN-RND Affiliated Partner)
    Cerebellum (London, England) · DOI · Europe PMC
  • 2026-09综述
    Adaptor protein complex 5 (AP-5) and the SPG11-SPG15 coat-like machinery in endolysosomal retrograde trafficking and human disease: A review
    International journal of biological macromolecules · DOI · Europe PMC
  • 2026-09病例报告开放获取
    A Novel KCNA1 Variant in a Patient With Tremor and Autism Spectrum Disorder Causes Mixed LOF/GOF Defects of Kv1.1 Channels
    Annals of clinical and translational neurology · DOI · Europe PMC
  • 2026-09综述
    Phenotypic Spectrum and Clinical Approach to Early-Onset Hereditary Spastic Paraplegia
    Movement disorders clinical practice · DOI · Europe PMC
  • 2026-09
    Defective ATP13A2-ITCH-ALIX signaling impairs intraluminal vesicle biogenesis and increases neuronal vulnerability
    Cellular signalling · DOI · Europe PMC
  • 2026-09病例报告
    Expanding the adult spectrum of TUBB4A disease: a spasticity-tremor phenotype with network imaging correlates
    Neurogenetics · DOI · Europe PMC
  • 2026-09开放获取
    Spectrum of Hereditary Ataxia in Omani Children
    Journal of clinical medicine · DOI · Europe PMC
  • 2026-09开放获取
    Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria
    Nature communications · DOI · Europe PMC
  • 2026-09
    Localized disruption of the presynaptic endoplasmic reticulum in Atlastin mutants
    Journal of cell science · DOI · Europe PMC
  • 2026-09系统综述综述病例报告开放获取
    Progressive Spastic Paraparesis Caused by Thoracic Spinal Epidural Lipomatosis: A Case Report and Systematic Review
    Medical sciences (Basel, Switzerland) · DOI · Europe PMC
  • 2026-09综述
    Lipid flip-flop in biological membranes: through the lens of TMEM16F
    Physiological reviews · DOI · Europe PMC
  • 2026-09病例报告
    "Ears of the lynx" sign on MRI: A radiologic clue to hereditary spastic paraplegia
    Radiology case reports · DOI · Europe PMC
  • 2026-09病例报告开放获取
    “Ears of the lynx” sign on MRI: A radiologic clue to hereditary spastic paraplegia
    Radiology case reports
  • 2026-09开放获取
    Multivariate Characterization of Gait Variability Under Simulated Ship Roll Motion
    Bioengineering (Basel, Switzerland) · DOI · Europe PMC
  • 2026-09病例报告
    Cognitive impairment as a manifestation of SPG7: case report
    Neurocase · 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。

尚未获批的在研药物（1 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。

  • adeno-associated virus serotype 9 gene transfer vector expressing huma美国2021-02-16
    Treatment of hereditary spastic paraplegia 47
    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 5L2

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 3

  • 招募中NCT06478238
    Calcium Folinate Treatment of Spastic Paraplegia 56
    早期 I 期 · 干预性 · 2024/07/01Shanghai 6th People's Hospital
    中国研究中心 1 个：Shanghai
  • 招募中NCT06844734
    A Prospective Cohort Study of ITB Treatment for HSP
    观察性 · 2025/01/01Shanghai 6th People's Hospital
    中国研究中心 1 个：Shanghai
  • 招募中NCT06936163
    A Prospective Cohort Study of Surgical Treatment for Foot Deformities in HSP
    观察性 · 2025/03/01Shanghai 6th People's Hospital
    中国研究中心 1 个：Shanghai
其他状态的试验（2 项）
  • 状态未知NCT04101643
    PCSK9 Inhibitor Treatment for Patients With SPG5
    I 期、II 期 · 干预性 · 2019/09/29First Affiliated Hospital of Fujian Medical University
    中国研究中心 1 个：Fuzhou
  • 状态未知NCT05196178
    Spinal Cord Stimulation Therapy for Hereditary Spastic Paraplegias Patients
    不适用 · 干预性 · 2021/11/15Xuanwu Hospital, Beijing
    中国研究中心 1 个：Beijing

中国境外的在招试验 22L2

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10意大利5德国3西班牙2奥地利2法国2捷克1爱尔兰1荷兰1波兰1比利时1加拿大1

CT.gov 报告命中 22 项，此处取回并展示最近的 15 项。

  • 招募中NCT07417943
    Neuromodulation to Enhance Motor Function in HSP
    不适用 · 干预性 · 2026/04/09Rahul Sachdeva
    美国
  • 招募中NCT06692712
    Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.
    III 期 · 干预性 · 2026/04/01Elpida Therapeutics SPC
    西班牙、美国
  • 招募中NCT07478172
    Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
    不适用 · 干预性 · 2026/03/10University of Missouri-Columbia
    美国
  • 尚未开始招募NCT06948019
    Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
    I 期、II 期 · 干预性 · 2025/08BlackfinBio Ltd
    美国
  • 招募中NCT06742697
    Flexibility, Resistance, Aerobic, Movement Execution Training in Adults With Hereditary Spastic Paraplegia
    不适用 · 干预性 · 2024/12/23IRCCS Eugenio Medea
    意大利
  • 招募中NCT07798674
    TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias
    观察性 · 2024/07/16Heidelberg University
    奥地利、捷克、法国、德国、爱尔兰、意大利、荷兰、波兰 等 9 国
  • 招募中NCT06553976
    Spastic Paraplegia - Centers of Excellence Research Network
    观察性 · 2024/06/04Boston Children's Hospital
    美国
  • 招募中NCT06229626
    Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
    不适用 · 干预性 · 2024/04/04Assistance Publique - Hôpitaux de Paris
    法国
  • 招募中NCT07136844
    Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
    不适用 · 干预性 · 2024/03/29Centre Hospitalier Universitaire de Liege
    比利时
  • 招募中NCT06572046
    STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
    观察性 · 2024/01/24IRCCS Fondazione Stella Maris
    意大利
  • 招募中NCT06092346
    A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders
    观察性 · 2023/12/19National Human Genome Research Institute (NHGRI)
    美国
  • 招募中NCT05848271
    Natural History Study of Patients with HPDL Mutations
    观察性 · 2023/05/18University of California, San Diego
    美国
  • 招募中NCT07090057
    The Effect of Targeting the Plantaris Muscle-tendon in Surgical Correction of Ankle Equinus in Children
    不适用 · 干预性 · 2023/03/13University of Alberta
    加拿大
  • 招募中NCT05518188
    Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
    I 期、II 期 · 干预性 · 2023/02/15Elpida Therapeutics SPC
    美国
  • 招募中NCT05354622
    Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
    观察性 · 2022/04/25Boston Children's Hospital
    美国

外部标识与链接

OrphanetMONDO:0019064MONDO:19064GARD:6637ICD-10 G11.4ICD-11 8B44.0ClinicalTrials.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）