CPT1C-Related Hereditary Spastic Paraplegia

Mendelian MONDO:0014568 Pathograph 5 Show in embeddings browser Hereditary Spastic Paraplegia

CPT1C-related hereditary spastic paraplegia (SPG73) is a rare, pure autosomal dominant form of hereditary spastic paraplegia caused by a heterozygous variant in CPT1C, the gene encoding the neuronal (brain-specific) isoform of carnitine palmitoyltransferase 1. Unlike the liver (CPT1A) and muscle (CPT1B) isozymes, CPT1C localizes to the endoplasmic reticulum rather than the mitochondrion, is expressed predominantly in neurons, and has little or no enzymatic activity in fatty acid oxidation; it instead participates in the ER protein-interaction network (including atlastin-1/ATL1, the SPG3A protein) that shapes the tubular ER and regulates neuronal lipid-droplet biogenesis. The disease was first defined in a three-generation southern Italian family carrying the c.109C>T (p.Arg37Cys) substitution, which strictly cosegregated with disease and impairs lipid-droplet formation, apparently through a dominant-negative mechanism. Clinically it presents as slowly progressive, adult-onset, pure spastic paraparesis of the lower limbs (spasticity, hyperreflexia, extensor plantar responses, mild weakness) with normal cognition and normal peripheral nerve conduction, reflecting a length-dependent distal axonopathy of the corticospinal tract. Because the disease is placed within the carnitine-cycle/fatty-acid metabolism family by gene homology (a CPT1 isoform) but manifests as a neurodegenerative corticospinal disorder rather than a systemic fatty-acid oxidation defect, it is curated here as a distinct entry rather than folded into the hepatic/muscle carnitine palmitoyltransferase deficiencies.

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1
Mappings
1
Inheritance
4
Pathophys.
5
Phenotypes
5
Pathograph
1
Genes
3
Medical Actions
1
References
🔗

Mappings

MONDO
MONDO:0014568 hereditary spastic paraplegia 73
skos:exactMatch MONDO
👪

Inheritance

1
Autosomal dominant HP:0000006
Autosomal dominant inheritance; the reported c.109C>T (p.Arg37Cys) CPT1C variant cosegregated with disease across an affected three-generation family and is proposed to act through a dominant-negative mechanism.
Autosomal dominant inheritance
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"This variant was also absent in the other unaffected participants (III-1, IV-2, and IV-3), thus strictly cosegregating with the disease phenotype."
The CPT1C variant cosegregated with disease in an autosomal dominant pedigree.
⚙

Pathophysiology

4
CPT1C Dysfunction (Neuronal ER Isoform)
A heterozygous CPT1C variant (p.Arg37Cys) alters the neuronal, ER-localized isoform of carnitine palmitoyltransferase 1. CPT1C differs from the mitochondrial CPT1A/CPT1B isozymes: it localizes to the endoplasmic reticulum, is expressed mainly in neurons, and has little or no fatty-acid-oxidation activity, so the lesion is a neuronal ER-protein defect rather than a classic carnitine-cycle fatty-acid oxidation block.
CPT1C hgnc:18540 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves CPT1C (hgnc:18540). hgnc:18540 is a gene from the HUGO Gene Nomenclature Committee.
Downstream
Disrupted ER Protein-Interaction Network Altered CPT1C perturbs the ER protein-interaction network that shapes the tubular endoplasmic reticulum in neurons.
Show evidence (2 references)
PMID:25751282 SUPPORT Human Clinical
"we identified a mutation in the neuronal isoform of the carnitine palmitoyl-transferase (CPT1C) gene as the genetic cause of a pure AD-HSP, termed hereditary spastic paraplegia type 73 (SPG73)"
A CPT1C mutation is the genetic cause of SPG73.
PMID:25751282 SUPPORT In Vitro
"It localizes to the ER and not to the mitochondria11 and has little or no enzymatic activity in fatty acid oxidation."
Establishes that CPT1C is ER-localized and lacks fatty-acid-oxidation activity, distinguishing it from CPT1A/CPT1B.
Disrupted ER Protein-Interaction Network
CPT1C is part of the endoplasmic reticulum protein-interaction network that shapes the tubular ER; it interacts with atlastin-1 (ATL1, the SPG3A protein), linking CPT1C to the same ER-morphogenesis machinery implicated in other pure hereditary spastic paraplegias. Perturbation of this network is a recurrent HSP pathogenic theme.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
endoplasmic reticulum organization GO:0007029 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal endoplasmic reticulum organization (GO:0007029). GO:0007029 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Impaired Neuronal Lipid Droplet Biogenesis Disruption of the CPT1C/atlastin-1 ER network impairs neuronal lipid-droplet formation.
Show evidence (1 reference)
PMID:25751282 SUPPORT In Vitro
"We show that CPT1C is expressed in motor neurons and interacts with atlastin-1, the protein encoded by the ATL1 gene."
CPT1C interacts with the ER-shaping protein atlastin-1 (SPG3A), placing it in the HSP ER-network.
Impaired Neuronal Lipid Droplet Biogenesis
Mutant CPT1C markedly reduces the number and size of lipid droplets in transfected cells, and Cpt1c-null cortical neurons show reduced lipid droplets, supporting a dominant-negative effect on lipid-droplet formation and altered lipid-mediated signaling in neurons.
neuron CL:0000540 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neuron (CL:0000540). CL:0000540 is a cell type from the Cell Ontology.
lipid droplet formation GO:0140042 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased lipid droplet formation (GO:0140042). GO:0140042 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Corticospinal Tract Axonal Degeneration Impaired neuronal lipid-droplet metabolism is proposed to compromise the integrity of long corticospinal axons.
Show evidence (2 references)
PMID:25751282 SUPPORT In Vitro
"We showed that mutant CPT1C markedly reduces the number and size of LDs in transfected cells."
Mutant CPT1C impairs lipid-droplet biogenesis in a cellular model.
PMID:25751282 SUPPORT Model Organism
"cortical neurons derived from Cpt1c−/− mice23,27 similarly exhibited a marked reduction in the number of LDs, suggesting a dominant negative mechanism for the Arg37Cys mutation"
Cpt1c-null mouse cortical neurons recapitulate the lipid-droplet reduction, supporting a dominant-negative mechanism.
Corticospinal Tract Axonal Degeneration
Convergent ER/lipid dysfunction in corticospinal motor neurons is proposed to compromise the integrity of their long axons, producing the length-dependent distal corticospinal-tract axonopathy that underlies the spastic paraparesis of hereditary spastic paraplegia. Neurophysiology in affected individuals showed prolonged central motor conduction with normal peripheral nerve conduction, localizing the lesion to the corticospinal tract (and dorsal columns).
upper motor neuron CL:0008048 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves upper motor neuron (CL:0008048). CL:0008048 is a cell type from the Cell Ontology.
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"indicating abnormalities of the corticospinal tract and the dorsal column. Peripheral nerve conduction velocities were normal in all participants examined"
Neurophysiology localizes the SPG73 lesion to the corticospinal tract with intact peripheral nerves, consistent with a central distal axonopathy.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for CPT1C-Related Hereditary Spastic Paraplegia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Musculoskeletal 1
Spastic paraplegia HP:0001258 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Spastic paraplegia (HP:0001258), qualified as course progressive; young adult onset. HP:0001258 is a phenotype from the Human Phenotype Ontology.
Course: PROGRESSIVE Onset: YOUNG ADULT
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"We identified a 3-generation family from southern Italy with dominantly inherited, adult-onset, and pure spastic paraplegia of unknown genetic cause"
Affected individuals present with adult-onset pure spastic paraplegia.
Other 4
Lower limb spasticity HP:0002061 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lower limb spasticity (HP:0002061). HP:0002061 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"adult-onset, and pure spastic paraplegia of unknown genetic cause"
The pure spastic paraplegia phenotype includes lower-limb spasticity.
Progressive gait impairment Spastic gait HP:0002064 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Spastic gait (HP:0002064), qualified as course progressive. HP:0002064 is a phenotype from the Human Phenotype Ontology.
Course: PROGRESSIVE
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"The disease was slowly progressive, leading to impairment or loss of ambulation 10 to 15 years after the onset of symptoms."
Progressive spastic gait impairment leading to loss of ambulation.
Lower limb hyperreflexia HP:0002395 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lower limb hyperreflexia (HP:0002395). HP:0002395 is a phenotype from the Human Phenotype Ontology.
Babinski sign HP:0003487 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Babinski sign (HP:0003487). HP:0003487 is a phenotype from the Human Phenotype Ontology.
🧬

Genetic Associations

1
CPT1C pathogenic variant (Causative)
Gene: CPT1C hgnc:18540 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CPT1C (hgnc:18540). hgnc:18540 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:25751282 SUPPORT Human Clinical
"In this study, we showed that the mutation Arg37Cys in the ER protein CPT1C causes a pure form of AD-HSP (SPG73)."
Identifies the causal CPT1C p.Arg37Cys variant for SPG73.
💊

Medical Actions

3
Supportive and symptomatic care
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
No disease-modifying therapy exists; management is supportive, focused on reducing lower-limb spasticity and maintaining mobility, as for other pure hereditary spastic paraplegias.
Physical therapy
Action: physical therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is physical therapy (NCIT:C15302). NCIT:C15302 is a clinical intervention from the NCI Thesaurus. Ontology label: Physical Therapy NCIT:C15302
Physiotherapy and stretching to manage spasticity, preserve range of motion, and maintain ambulation.
Antispasticity pharmacotherapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: baclofen CHEBI:2972 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses baclofen (CHEBI:2972). CHEBI:2972 is a therapeutic agent from Chemical Entities of Biological Interest.
Symptomatic anti-spasticity agents (e.g., baclofen) are used to reduce lower-limb spasticity in hereditary spastic paraplegia.
{ }

Source YAML

click to show 
name: CPT1C-Related Hereditary Spastic Paraplegia
creation_date: "2026-07-07T00:00:00Z"
description: >-
  CPT1C-related hereditary spastic paraplegia (SPG73) is a rare, pure autosomal
  dominant form of hereditary spastic paraplegia caused by a heterozygous variant
  in CPT1C, the gene encoding the neuronal (brain-specific) isoform of carnitine
  palmitoyltransferase 1. Unlike the liver (CPT1A) and muscle (CPT1B) isozymes,
  CPT1C localizes to the endoplasmic reticulum rather than the mitochondrion, is
  expressed predominantly in neurons, and has little or no enzymatic activity in
  fatty acid oxidation; it instead participates in the ER protein-interaction
  network (including atlastin-1/ATL1, the SPG3A protein) that shapes the tubular
  ER and regulates neuronal lipid-droplet biogenesis. The disease was first
  defined in a three-generation southern Italian family carrying the c.109C>T
  (p.Arg37Cys) substitution, which strictly cosegregated with disease and impairs
  lipid-droplet formation, apparently through a dominant-negative mechanism.
  Clinically it presents as slowly progressive, adult-onset, pure spastic
  paraparesis of the lower limbs (spasticity, hyperreflexia, extensor plantar
  responses, mild weakness) with normal cognition and normal peripheral nerve
  conduction, reflecting a length-dependent distal axonopathy of the corticospinal
  tract. Because the disease is placed within the carnitine-cycle/fatty-acid
  metabolism family by gene homology (a CPT1 isoform) but manifests as a
  neurodegenerative corticospinal disorder rather than a systemic fatty-acid
  oxidation defect, it is curated here as a distinct entry rather than folded into
  the hepatic/muscle carnitine palmitoyltransferase deficiencies.
synonyms:
- SPG73
- Hereditary spastic paraplegia 73
- CPT1C-related autosomal dominant pure spastic paraplegia
- Autosomal dominant spastic paraplegia type 73
category: Mendelian
disease_term:
  preferred_term: hereditary spastic paraplegia 73
  term:
    id: MONDO:0014568
    label: hereditary spastic paraplegia 73
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0014568
      label: hereditary spastic paraplegia 73
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
parents:
- Hereditary Spastic Paraplegia
inheritance:
- name: Autosomal dominant
  description: >-
    Autosomal dominant inheritance; the reported c.109C>T (p.Arg37Cys) CPT1C
    variant cosegregated with disease across an affected three-generation family
    and is proposed to act through a dominant-negative mechanism.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This variant was also absent in the other unaffected participants (III-1, IV-2, and IV-3), thus strictly cosegregating with the disease phenotype."
    explanation: The CPT1C variant cosegregated with disease in an autosomal dominant pedigree.
pathophysiology:
- name: CPT1C Dysfunction (Neuronal ER Isoform)
  conforms_to: "corticospinal_tract_axonopathy#Long-Axon Maintenance Machinery Defect"
  description: >-
    A heterozygous CPT1C variant (p.Arg37Cys) alters the neuronal, ER-localized
    isoform of carnitine palmitoyltransferase 1. CPT1C differs from the mitochondrial
    CPT1A/CPT1B isozymes: it localizes to the endoplasmic reticulum, is expressed
    mainly in neurons, and has little or no fatty-acid-oxidation activity, so the
    lesion is a neuronal ER-protein defect rather than a classic carnitine-cycle
    fatty-acid oxidation block.
  gene:
    preferred_term: CPT1C
    term:
      id: hgnc:18540
      label: CPT1C
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we identified a mutation in the neuronal isoform of the carnitine palmitoyl-transferase (CPT1C) gene as the genetic cause of a pure AD-HSP, termed hereditary spastic paraplegia type 73 (SPG73)"
    explanation: A CPT1C mutation is the genetic cause of SPG73.
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "It localizes to the ER and not to the mitochondria11 and has little or no enzymatic activity in fatty acid oxidation."
    explanation: Establishes that CPT1C is ER-localized and lacks fatty-acid-oxidation activity, distinguishing it from CPT1A/CPT1B.
  downstream:
  - target: Disrupted ER Protein-Interaction Network
    description: >-
      Altered CPT1C perturbs the ER protein-interaction network that shapes the
      tubular endoplasmic reticulum in neurons.
- name: Disrupted ER Protein-Interaction Network
  description: >-
    CPT1C is part of the endoplasmic reticulum protein-interaction network that
    shapes the tubular ER; it interacts with atlastin-1 (ATL1, the SPG3A protein),
    linking CPT1C to the same ER-morphogenesis machinery implicated in other pure
    hereditary spastic paraplegias. Perturbation of this network is a recurrent
    HSP pathogenic theme.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: endoplasmic reticulum organization
    term:
      id: GO:0007029
      label: endoplasmic reticulum organization
    modifier: ABNORMAL
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "We show that CPT1C is expressed in motor neurons and interacts with atlastin-1, the protein encoded by the ATL1 gene."
    explanation: CPT1C interacts with the ER-shaping protein atlastin-1 (SPG3A), placing it in the HSP ER-network.
  downstream:
  - target: Impaired Neuronal Lipid Droplet Biogenesis
    description: >-
      Disruption of the CPT1C/atlastin-1 ER network impairs neuronal lipid-droplet
      formation.
- name: Impaired Neuronal Lipid Droplet Biogenesis
  description: >-
    Mutant CPT1C markedly reduces the number and size of lipid droplets in
    transfected cells, and Cpt1c-null cortical neurons show reduced lipid droplets,
    supporting a dominant-negative effect on lipid-droplet formation and altered
    lipid-mediated signaling in neurons.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  biological_processes:
  - preferred_term: lipid droplet formation
    term:
      id: GO:0140042
      label: lipid droplet formation
    modifier: DECREASED
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "We showed that mutant CPT1C markedly reduces the number and size of LDs in transfected cells."
    explanation: Mutant CPT1C impairs lipid-droplet biogenesis in a cellular model.
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "cortical neurons derived from Cpt1c−/− mice23,27 similarly exhibited a marked reduction in the number of LDs, suggesting a dominant negative mechanism for the Arg37Cys mutation"
    explanation: Cpt1c-null mouse cortical neurons recapitulate the lipid-droplet reduction, supporting a dominant-negative mechanism.
  downstream:
  - target: Corticospinal Tract Axonal Degeneration
    description: >-
      Impaired neuronal lipid-droplet metabolism is proposed to compromise the
      integrity of long corticospinal axons.
- name: Corticospinal Tract Axonal Degeneration
  conforms_to: "corticospinal_tract_axonopathy#Distal Length-Dependent Degeneration of Long CNS Axons"
  description: >-
    Convergent ER/lipid dysfunction in corticospinal motor neurons is proposed to
    compromise the integrity of their long axons, producing the length-dependent
    distal corticospinal-tract axonopathy that underlies the spastic paraparesis of
    hereditary spastic paraplegia. Neurophysiology in affected individuals showed
    prolonged central motor conduction with normal peripheral nerve conduction,
    localizing the lesion to the corticospinal tract (and dorsal columns).
  cell_types:
  - preferred_term: upper motor neuron
    term:
      id: CL:0008048
      label: upper motor neuron
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "indicating abnormalities of the corticospinal tract and the dorsal column. Peripheral nerve conduction velocities were normal in all participants examined"
    explanation: Neurophysiology localizes the SPG73 lesion to the corticospinal tract with intact peripheral nerves, consistent with a central distal axonopathy.
phenotypes:
- name: Spastic paraplegia
  category: Neurological
  description: >-
    Pure, slowly progressive lower-limb spastic paraparesis is the defining
    manifestation of SPG73, with adult onset.
  phenotype_term:
    preferred_term: Spastic paraplegia
    term:
      id: HP:0001258
      label: Spastic paraplegia
    clinical_course: PROGRESSIVE
    onset:
      onset_category: YOUNG_ADULT
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identified a 3-generation family from southern Italy with dominantly inherited, adult-onset, and pure spastic paraplegia of unknown genetic cause"
    explanation: Affected individuals present with adult-onset pure spastic paraplegia.
- name: Lower limb spasticity
  category: Neurological
  description: Spasticity of the lower extremities.
  phenotype_term:
    preferred_term: Lower limb spasticity
    term:
      id: HP:0002061
      label: Lower limb spasticity
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "adult-onset, and pure spastic paraplegia of unknown genetic cause"
    explanation: The pure spastic paraplegia phenotype includes lower-limb spasticity.
- name: Progressive gait impairment
  category: Neurological
  description: >-
    The disease is slowly progressive, leading to impairment or loss of ambulation
    over 10 to 15 years, reflecting progressive spastic gait impairment from
    corticospinal tract involvement.
  phenotype_term:
    preferred_term: Spastic gait
    term:
      id: HP:0002064
      label: Spastic gait
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The disease was slowly progressive, leading to impairment or loss of ambulation 10 to 15 years after the onset of symptoms."
    explanation: Progressive spastic gait impairment leading to loss of ambulation.
- name: Lower limb hyperreflexia
  category: Neurological
  description: >-
    Increased lower-limb deep tendon reflexes, a cardinal upper motor neuron sign of
    corticospinal tract involvement in hereditary spastic paraplegia.
  phenotype_term:
    preferred_term: Lower limb hyperreflexia
    term:
      id: HP:0002395
      label: Lower limb hyperreflexia
- name: Babinski sign
  category: Neurological
  description: >-
    Extensor plantar response (Babinski sign) reflecting upper motor neuron
    dysfunction and corticospinal tract damage, documented in affected family members
    on neurological examination.
  phenotype_term:
    preferred_term: Babinski sign
    term:
      id: HP:0003487
      label: Babinski sign
genetic:
- name: CPT1C pathogenic variant
  gene_term:
    preferred_term: CPT1C
    term:
      id: hgnc:18540
      label: CPT1C
  association: Causative
  notes: >-
    Heterozygous CPT1C c.109C>T (p.Arg37Cys) in exon 3 was identified by
    whole-exome sequencing with linkage in a three-generation family; the variant
    was absent from control databases and 712 additional control exomes, strictly
    cosegregated with disease, and was predicted damaging. CPT1C encodes the
    neuronal ER-localized isoform of carnitine palmitoyltransferase 1.
  evidence:
  - reference: PMID:25751282
    reference_title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In this study, we showed that the mutation Arg37Cys in the ER protein CPT1C causes a pure form of AD-HSP (SPG73)."
    explanation: Identifies the causal CPT1C p.Arg37Cys variant for SPG73.
treatments:
- name: Supportive and symptomatic care
  description: >-
    No disease-modifying therapy exists; management is supportive, focused on
    reducing lower-limb spasticity and maintaining mobility, as for other pure
    hereditary spastic paraplegias.
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
- name: Physical therapy
  description: >-
    Physiotherapy and stretching to manage spasticity, preserve range of motion,
    and maintain ambulation.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
- name: Antispasticity pharmacotherapy
  description: >-
    Symptomatic anti-spasticity agents (e.g., baclofen) are used to reduce
    lower-limb spasticity in hereditary spastic paraplegia.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: baclofen
      term:
        id: CHEBI:2972
        label: baclofen
references:
- reference: PMID:25751282
  title: "Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia."
  findings: []
📚

References & Deep Research

References

1
PMID:25751282
Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia.
No top-level findings curated for this source.