EEFSEC Deficiency

Metabolic Disorder Pathograph 4 Show in embeddings browser Selenoprotein Biosynthesis Disorder Trace Element Metabolism Disorder

EEFSEC deficiency is an autosomal recessive selenoprotein synthesis disorder caused by biallelic EEFSEC variants. EEFSEC encodes the specialized selenocysteine-tRNA-specific eukaryotic elongation factor eEFSec, which promotes selenocysteinyl-tRNA delivery for UGA recoding during selenoprotein translation. Reduced EEFSEC function lowers selenoprotein levels, especially demonstrable in fibroblasts, and causes early-onset progressive neurodegeneration with global developmental delay, spasticity, ataxia, seizures, and cerebellar hypoplasia/atrophy.

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1
Inheritance
3
Pathophys.
6
Phenotypes
4
Pathograph
1
Genes
🏷

Classifications

👪

Inheritance

1
Autosomal Recessive HP:0000007
Autosomal recessive inheritance
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures."
Directly states autosomal recessive inheritance for EEFSEC deficiency.
⚙

Pathophysiology

3
EEFSEC-dependent Sec-tRNA elongation defect
EEFSEC/eEFSec is the specialized translation elongation factor that promotes selenocysteine incorporation into selenoproteins. Pathogenic variants impair this elongation-stage Sec-tRNA delivery mechanism.
EEFSEC hgnc:24614
translational elongation GO:0006414 ↓ DECREASED selenocysteine incorporation GO:0001514 ↓ DECREASED
Downstream
Reduced fibroblast selenoprotein levels Reduced EEFSEC function lowers cellular selenoprotein levels.
Show evidence (1 reference)
PMID:27708257 SUPPORT In Vitro
"A specialized translation elongation factor, eEFSec in eukaryotes and SelB in prokaryotes, promotes selenocysteine incorporation into selenoproteins by a still poorly understood mechanism."
Defines the elongation-factor role of eEFSec in selenocysteine incorporation.
Reduced fibroblast selenoprotein levels
EEFSEC variants reduce EEFSEC activity and lower selenoprotein levels in patient-derived fibroblasts, confirming impaired selenoprotein synthesis at the cellular level.
fibroblast CL:0000057
selenocysteine incorporation GO:0001514 ↓ DECREASED
Downstream
Progressive neurodegeneration Selenoprotein deficiency manifests clinically as progressive neurodegeneration with cerebellar pathology.
Show evidence (1 reference)
PMID:39753114 SUPPORT In Vitro
"leading to lower levels of selenoproteins in fibroblasts."
Supports decreased selenoprotein levels in fibroblasts from affected individuals.
Progressive neurodegeneration
EEFSEC deficiency causes progressive neurodegeneration with prominent cerebellar involvement, including cerebellar hypoplasia and progressive atrophy on MRI.
neuron CL:0000540 glial cell CL:0000125
brain UBERON:0000955 cerebellum UBERON:0002037
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy."
Supports cerebellar neurodegenerative pathology in EEFSEC deficiency.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for EEFSEC Deficiency 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

6
Musculoskeletal 1
Progressive spasticity Spasticity HP:0001257
Course: PROGRESSIVE
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures."
Supports progressive spasticity in EEFSEC deficiency.
Nervous System 5
Global developmental delay Global developmental delay HP:0001263
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures."
Supports global developmental delay in EEFSEC deficiency.
Ataxia Ataxia HP:0001251
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures."
Supports ataxia in EEFSEC deficiency.
Seizure Seizure HP:0001250
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures."
Supports seizures in EEFSEC deficiency.
Cerebellar hypoplasia Cerebellar hypoplasia HP:0001321
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy."
Supports cerebellar hypoplasia in EEFSEC deficiency.
Progressive cerebellar atrophy Cerebellar atrophy HP:0001272
Course: PROGRESSIVE
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy."
Supports progressive cerebellar atrophy in EEFSEC deficiency.
🧬

Genetic Associations

1
EEFSEC pathogenic variants (Loss-of-function)
Gene: EEFSEC hgnc:24614
Show evidence (1 reference)
PMID:39753114 SUPPORT Human Clinical
"Exome or genome sequencing identified six different bi-allelic EEFSEC variants in nine individuals from eight unrelated families."
Supports biallelic EEFSEC variants as the causal genetic basis.
{ }

Source YAML

click to show 
name: EEFSEC Deficiency
creation_date: "2026-07-06T05:15:58Z"
category: Metabolic Disorder
parents:
- Selenoprotein Biosynthesis Disorder
- Trace Element Metabolism Disorder
description: >-
  EEFSEC deficiency is an autosomal recessive selenoprotein synthesis disorder
  caused by biallelic EEFSEC variants. EEFSEC encodes the specialized
  selenocysteine-tRNA-specific eukaryotic elongation factor eEFSec, which
  promotes selenocysteinyl-tRNA delivery for UGA recoding during selenoprotein
  translation. Reduced EEFSEC function lowers selenoprotein levels, especially
  demonstrable in fibroblasts, and causes early-onset progressive
  neurodegeneration with global developmental delay, spasticity, ataxia,
  seizures, and cerebellar hypoplasia/atrophy.
synonyms:
- EEFSEC-related selenopathy with early-onset neurodegeneration
- eEFSec deficiency
- selenocysteine tRNA-specific eukaryotic elongation factor deficiency
notes: >-
  WP-079 seed identifier OMIM:607695 is an EEFSEC gene/locus record rather than
  a disease phenotype record. No exact local MONDO disease term was resolved, so
  disease_term is intentionally left unbound.
classifications:
  icimd_category:
  - classification_value: trace_element_other
    notes: >-
      ICIMD category 22, "Disorders of trace elements and metals", other
      trace-element metabolism. EEFSEC deficiency is a selenocysteine metabolism
      disorder that impairs selenoprotein synthesis.
    evidence:
    - reference: PMID:39753114
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        This study identifies EEFSEC deficiency as an inborn error of
        selenocysteine metabolism.
      explanation: >-
        Supports classifying EEFSEC deficiency as a trace-element/selenocysteine
        metabolism disorder.
inheritance:
- name: Autosomal Recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFSEC deficiency, an autosomal recessive disorder, manifests with global
      developmental delay, progressive spasticity, ataxia, and seizures.
    explanation: >-
      Directly states autosomal recessive inheritance for EEFSEC deficiency.
genetic:
- name: EEFSEC pathogenic variants
  gene_term:
    preferred_term: EEFSEC
    term:
      id: hgnc:24614
      label: EEFSEC
  association: Loss-of-function
  presence: Positive
  notes: >-
    Biallelic EEFSEC variants reduce activity of the specialized elongation
    factor required for Sec-tRNA delivery during selenoprotein translation.
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Exome or genome sequencing identified six different bi-allelic EEFSEC
      variants in nine individuals from eight unrelated families.
    explanation: >-
      Supports biallelic EEFSEC variants as the causal genetic basis.
pathophysiology:
- name: EEFSEC-dependent Sec-tRNA elongation defect
  description: >-
    EEFSEC/eEFSec is the specialized translation elongation factor that promotes
    selenocysteine incorporation into selenoproteins. Pathogenic variants impair
    this elongation-stage Sec-tRNA delivery mechanism.
  genes:
  - preferred_term: EEFSEC
    term:
      id: hgnc:24614
      label: EEFSEC
  biological_processes:
  - preferred_term: translational elongation
    term:
      id: GO:0006414
      label: translational elongation
    modifier: DECREASED
  - preferred_term: selenocysteine incorporation
    term:
      id: GO:0001514
      label: selenocysteine incorporation
    modifier: DECREASED
  chemical_entities:
  - preferred_term: selenocysteine
    term:
      id: CHEBI:9093
      label: selenocysteine
  evidence:
  - reference: PMID:27708257
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      A specialized translation elongation factor, eEFSec in eukaryotes and SelB
      in prokaryotes, promotes selenocysteine incorporation into selenoproteins
      by a still poorly understood mechanism.
    explanation: >-
      Defines the elongation-factor role of eEFSec in selenocysteine
      incorporation.
  downstream:
  - target: Reduced fibroblast selenoprotein levels
    description: >-
      Reduced EEFSEC function lowers cellular selenoprotein levels.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:39753114
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: leading to lower levels of selenoproteins in fibroblasts.
      explanation: >-
        Supports reduced cellular selenoprotein levels downstream of EEFSEC
        dysfunction.
- name: Reduced fibroblast selenoprotein levels
  description: >-
    EEFSEC variants reduce EEFSEC activity and lower selenoprotein levels in
    patient-derived fibroblasts, confirming impaired selenoprotein synthesis at
    the cellular level.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: selenocysteine incorporation
    term:
      id: GO:0001514
      label: selenocysteine incorporation
    modifier: DECREASED
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: leading to lower levels of selenoproteins in fibroblasts.
    explanation: >-
      Supports decreased selenoprotein levels in fibroblasts from affected
      individuals.
  downstream:
  - target: Progressive neurodegeneration
    description: >-
      Selenoprotein deficiency manifests clinically as progressive
      neurodegeneration with cerebellar pathology.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:39753114
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic
        elongation factor (EEFSEC) variants cause selenoprotein deficiency,
        leading to progressive neurodegeneration.
      explanation: >-
        Links EEFSEC variants and selenoprotein deficiency to progressive
        neurodegeneration.
- name: Progressive neurodegeneration
  description: >-
    EEFSEC deficiency causes progressive neurodegeneration with prominent
    cerebellar involvement, including cerebellar hypoplasia and progressive
    atrophy on MRI.
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  - preferred_term: glial cell
    term:
      id: CL:0000125
      label: glial cell
  locations:
  - preferred_term: brain
    term:
      id: UBERON:0000955
      label: brain
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cerebral MRI primarily demonstrated a cerebellar pathology, including
      hypoplasia and progressive atrophy.
    explanation: >-
      Supports cerebellar neurodegenerative pathology in EEFSEC deficiency.
phenotypes:
- name: Global developmental delay
  description: >-
    Global developmental delay is a core clinical manifestation.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFSEC deficiency, an autosomal recessive disorder, manifests with global
      developmental delay, progressive spasticity, ataxia, and seizures.
    explanation: >-
      Supports global developmental delay in EEFSEC deficiency.
- name: Progressive spasticity
  description: >-
    Spasticity progresses as part of the motor phenotype.
  phenotype_term:
    preferred_term: Spasticity
    term:
      id: HP:0001257
      label: Spasticity
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFSEC deficiency, an autosomal recessive disorder, manifests with global
      developmental delay, progressive spasticity, ataxia, and seizures.
    explanation: >-
      Supports progressive spasticity in EEFSEC deficiency.
- name: Ataxia
  description: >-
    Ataxia reflects cerebellar involvement.
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFSEC deficiency, an autosomal recessive disorder, manifests with global
      developmental delay, progressive spasticity, ataxia, and seizures.
    explanation: >-
      Supports ataxia in EEFSEC deficiency.
- name: Seizure
  description: >-
    Seizures are part of the early-onset neurodegenerative phenotype.
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      EEFSEC deficiency, an autosomal recessive disorder, manifests with global
      developmental delay, progressive spasticity, ataxia, and seizures.
    explanation: >-
      Supports seizures in EEFSEC deficiency.
- name: Cerebellar hypoplasia
  description: >-
    Brain MRI shows cerebellar hypoplasia.
  phenotype_term:
    preferred_term: Cerebellar hypoplasia
    term:
      id: HP:0001321
      label: Cerebellar hypoplasia
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cerebral MRI primarily demonstrated a cerebellar pathology, including
      hypoplasia and progressive atrophy.
    explanation: >-
      Supports cerebellar hypoplasia in EEFSEC deficiency.
- name: Progressive cerebellar atrophy
  description: >-
    Cerebellar atrophy progresses on MRI.
  phenotype_term:
    preferred_term: Cerebellar atrophy
    term:
      id: HP:0001272
      label: Cerebellar atrophy
    clinical_course: PROGRESSIVE
  evidence:
  - reference: PMID:39753114
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Cerebral MRI primarily demonstrated a cerebellar pathology, including
      hypoplasia and progressive atrophy.
    explanation: >-
      Supports progressive cerebellar atrophy in EEFSEC deficiency.