UGDH-related developmental and epileptic encephalopathy 84

Mendelian MONDO:0032918 Pathograph 4 Show in embeddings browser genetic developmental and epileptic encephalopathy congenital disorder of glycosylation

UGDH-related developmental and epileptic encephalopathy 84 is an autosomal recessive glycan-precursor disorder caused by biallelic loss-of-function variants in UGDH, which encodes UDP-glucose 6-dehydrogenase. Reduced UGDH activity limits conversion of UDP-glucose to UDP-glucuronic acid, decreasing the glucuronic-acid precursor pool needed for glycosaminoglycan, proteoglycan, and glycolipid production. The downstream disease is dominated by developmental and epileptic encephalopathy, hypotonia, motor disorder, developmental delay, intellectual disability, and variable brain growth or myelination abnormalities.

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

Classifications

👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
Affected individuals have biallelic germline UGDH variants consistent with autosomal recessive inheritance.
Autosomal recessive inheritance
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia."
The cohort directly establishes recessive UGDH mutations as the disease cause.
⚙

Pathophysiology

3
UGDH loss of function
Pathogenic biallelic UGDH variants reduce the stability, oligomerization, or catalytic activity of UDP-glucose 6-dehydrogenase.
UGDH hgnc:12525
UDP-glucose 6-dehydrogenase activity GO:0003979 ↓ DECREASED
Downstream
UDP-glucuronic acid precursor depletion Reduced UGDH activity decreases production of UDP-glucuronic acid from UDP-glucose.
Show evidence (1 reference)
PMID:32001716 SUPPORT In Vitro
"Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity."
Patient-cell and biochemical assays support reduced UGDH function as the proximal molecular defect.
UDP-glucuronic acid precursor depletion
UDP-glucuronic acid shortage impairs production of glycosaminoglycan-rich extracellular matrix components, including proteoglycans and glycolipids that are important in human brain development.
glycosaminoglycan biosynthetic process GO:0006024 ↓ DECREASED protein O-linked glycosylation GO:0006493 ⚠ ABNORMAL
Downstream
Neurodevelopmental and epileptic dysfunction Disrupted glycan-dependent extracellular matrix production impairs brain development and neuronal network function.
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development."
This supports the precursor-to-ECM branch of the pathograph.
Neurodevelopmental and epileptic dysfunction
The central nervous system phenotype includes developmental and epileptic encephalopathy, severe developmental delay, intellectual disability, hypotonia, and motor disorder.
neuron CL:0000540
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"All 30 patients carrying biallelic mutations in UGDH presented with a common core phenotype consisting of marked developmental delay, epilepsy, mild dysmorphism, and motor disorder with axial hypotonia"
The clinical cohort supports the recurrent neurologic consequence node.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for UGDH-related developmental and epileptic encephalopathy 84 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
Digestive 1
Dysphagia VERY_FREQUENT Dysphagia HP:0002015
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"Twenty-four out of the 30 (80%) were noted to have swallowing difficulties and gastrostomy tubes were required for feeding in 12 infants."
Swallowing difficulties in 24/30 patients equals 80%, which falls in the VERY_FREQUENT frequency band.
Musculoskeletal 1
Hypotonia Hypotonia HP:0001252
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"motor disorder with axial hypotonia"
The cohort directly reports axial hypotonia.
Nervous System 2
Global developmental delay Global developmental delay HP:0001263
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"common core phenotype consisting of marked developmental delay, epilepsy, mild dysmorphism, and motor disorder with axial hypotonia"
The cohort directly reports marked developmental delay.
Intellectual disability OBLIGATE Intellectual disability HP:0001249
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"A moderate to severe intellectual disability was observed in all patients."
The cohort reports intellectual disability in all patients, supporting the OBLIGATE frequency band for that cohort.
Other 2
Developmental and epileptic encephalopathy Epileptic encephalopathy HP:0200134
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"presenting with epileptic encephalopathy with developmental delay and hypotonia."
The cohort directly reports epileptic encephalopathy.
Infantile spasms FREQUENT Infantile spasms HP:0012469
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"Most patients have severe epilepsy ranging from neonatal onset developmental epileptic encephalopathy to infantile developmental epileptic encephalopathy (27 patients, 90%), of which 16 (53%) had infantile spasms"
Infantile spasms were reported in 16 patients, 53% of the cohort, which falls in the FREQUENT frequency band.
🧬

Genetic Associations

1
UGDH (Biallelic loss-of-function variants)
Gene: UGDH hgnc:12525 relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (1 reference)
PMID:32001716 SUPPORT Human Clinical
"Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia."
The cohort establishes UGDH as the causal gene for DEE84.
{ }

Source YAML

click to show 
name: UGDH-related developmental and epileptic encephalopathy 84
creation_date: "2026-07-06T06:04:18Z"
description: >-
  UGDH-related developmental and epileptic encephalopathy 84 is an autosomal
  recessive glycan-precursor disorder caused by biallelic loss-of-function
  variants in UGDH, which encodes UDP-glucose 6-dehydrogenase. Reduced UGDH
  activity limits conversion of UDP-glucose to UDP-glucuronic acid, decreasing
  the glucuronic-acid precursor pool needed for glycosaminoglycan,
  proteoglycan, and glycolipid production. The downstream disease is dominated
  by developmental and epileptic encephalopathy, hypotonia, motor disorder,
  developmental delay, intellectual disability, and variable brain growth or
  myelination abnormalities.
category: Mendelian
disease_term:
  preferred_term: developmental and epileptic encephalopathy, 84
  term:
    id: MONDO:0032918
    label: developmental and epileptic encephalopathy, 84
synonyms:
- DEE84
- EIEE84
- UGDH-related disorder
parents:
- genetic developmental and epileptic encephalopathy
- congenital disorder of glycosylation
classifications:
  icimd_category:
  - classification_value: multiple_glycosylation_pathways
    notes: >-
      Classified as a multiple-glycosylation-pathway disorder because UGDH
      controls UDP-glucuronic acid supply for glycosaminoglycan-containing
      proteoglycans and glycolipids.
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Affected individuals have biallelic germline UGDH variants consistent with
    autosomal recessive inheritance.
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, we report an allelic series of germline recessive mutations in UGDH
      in 36 cases from 25 families presenting with epileptic encephalopathy with
      developmental delay and hypotonia.
    explanation: >-
      The cohort directly establishes recessive UGDH mutations as the disease
      cause.
pathophysiology:
- name: UGDH loss of function
  description: >-
    Pathogenic biallelic UGDH variants reduce the stability, oligomerization, or
    catalytic activity of UDP-glucose 6-dehydrogenase.
  role: trigger
  genes:
  - preferred_term: UGDH
    term:
      id: hgnc:12525
      label: UGDH
  molecular_functions:
  - preferred_term: UDP-glucose 6-dehydrogenase activity
    modifier: DECREASED
    term:
      id: GO:0003979
      label: UDP-glucose 6-dehydrogenase activity
  chemical_entities:
  - preferred_term: UDP-D-glucose
    term:
      id: CHEBI:18066
      label: UDP-D-glucose
  - preferred_term: UDP-D-glucuronic acid
    modifier: DECREASED
    term:
      id: CHEBI:197331
      label: UDP-D-glucuronic acid
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Consistent with being loss-of-function alleles, we show using patients'
      primary fibroblasts and biochemical assays, that these mutations either
      impair UGDH stability, oligomerization, or enzymatic activity.
    explanation: >-
      Patient-cell and biochemical assays support reduced UGDH function as the
      proximal molecular defect.
  downstream:
  - target: UDP-glucuronic acid precursor depletion
    description: >-
      Reduced UGDH activity decreases production of UDP-glucuronic acid from
      UDP-glucose.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:32001716
      reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        UGDH encodes an oxidoreductase that converts UDP-glucose to
        UDP-glucuronic acid, a key component of specific proteoglycans and
        glycolipids.
      explanation: >-
        The abstract directly links UGDH enzymatic function to the
        UDP-glucuronic acid product.
- name: UDP-glucuronic acid precursor depletion
  description: >-
    UDP-glucuronic acid shortage impairs production of glycosaminoglycan-rich
    extracellular matrix components, including proteoglycans and glycolipids
    that are important in human brain development.
  role: central_effector
  biological_processes:
  - preferred_term: glycosaminoglycan biosynthetic process
    modifier: DECREASED
    term:
      id: GO:0006024
      label: glycosaminoglycan biosynthetic process
  - preferred_term: protein O-linked glycosylation
    modifier: ABNORMAL
    term:
      id: GO:0006493
      label: protein O-linked glycosylation
  chemical_entities:
  - preferred_term: glycosaminoglycan
    modifier: DECREASED
    term:
      id: CHEBI:18085
      label: glycosaminoglycan
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our study defines UGDH as a key player for the production of extracellular
      matrix components that are essential for human brain development.
    explanation: >-
      This supports the precursor-to-ECM branch of the pathograph.
  downstream:
  - target: Neurodevelopmental and epileptic dysfunction
    description: >-
      Disrupted glycan-dependent extracellular matrix production impairs brain
      development and neuronal network function.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - abnormal glycosaminoglycan-containing extracellular matrix
- name: Neurodevelopmental and epileptic dysfunction
  description: >-
    The central nervous system phenotype includes developmental and epileptic
    encephalopathy, severe developmental delay, intellectual disability,
    hypotonia, and motor disorder.
  role: consequence
  cell_types:
  - preferred_term: neuron
    term:
      id: CL:0000540
      label: neuron
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All 30 patients carrying biallelic mutations in UGDH presented with a
      common core phenotype consisting of marked developmental delay, epilepsy,
      mild dysmorphism, and motor disorder with axial hypotonia
    explanation: >-
      The clinical cohort supports the recurrent neurologic consequence node.
phenotypes:
- name: Developmental and epileptic encephalopathy
  description: >-
    Epileptic encephalopathy with developmental delay is the defining clinical
    presentation.
  phenotype_term:
    preferred_term: Epileptic encephalopathy
    term:
      id: HP:0200134
      label: Epileptic encephalopathy
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      presenting with epileptic encephalopathy with developmental delay and
      hypotonia.
    explanation: The cohort directly reports epileptic encephalopathy.
- name: Global developmental delay
  description: Developmental delay is part of the recurrent core phenotype.
  phenotype_term:
    preferred_term: Global developmental delay
    term:
      id: HP:0001263
      label: Global developmental delay
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      common core phenotype consisting of marked developmental delay, epilepsy,
      mild dysmorphism, and motor disorder with axial hypotonia
    explanation: The cohort directly reports marked developmental delay.
- name: Hypotonia
  description: Axial hypotonia is a core motor feature.
  phenotype_term:
    preferred_term: Hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      motor disorder with axial hypotonia
    explanation: The cohort directly reports axial hypotonia.
- name: Intellectual disability
  frequency: OBLIGATE
  description: Moderate to severe intellectual disability is reported in all affected individuals.
  phenotype_term:
    preferred_term: Intellectual disability
    term:
      id: HP:0001249
      label: Intellectual disability
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A moderate to severe intellectual disability was observed in all patients.
    explanation: >-
      The cohort reports intellectual disability in all patients, supporting the
      OBLIGATE frequency band for that cohort.
- name: Dysphagia
  frequency: VERY_FREQUENT
  description: Swallowing difficulties are common and may require gastrostomy feeding.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-four out of the 30 (80%) were noted to have swallowing difficulties
      and gastrostomy tubes were required for feeding in 12 infants.
    explanation: >-
      Swallowing difficulties in 24/30 patients equals 80%, which falls in the
      VERY_FREQUENT frequency band.
- name: Infantile spasms
  frequency: FREQUENT
  description: Infantile spasms are a frequent seizure type in UGDH-related DEE84.
  phenotype_term:
    preferred_term: Infantile spasms
    term:
      id: HP:0012469
      label: Infantile spasms
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most patients have severe epilepsy ranging from neonatal onset
      developmental epileptic encephalopathy to infantile developmental
      epileptic encephalopathy (27 patients, 90%), of which 16 (53%) had
      infantile spasms
    explanation: >-
      Infantile spasms were reported in 16 patients, 53% of the cohort, which
      falls in the FREQUENT frequency band.
genetic:
- name: UGDH
  association: Biallelic loss-of-function variants
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  gene_term:
    preferred_term: UGDH
    term:
      id: hgnc:12525
      label: UGDH
  evidence:
  - reference: PMID:32001716
    reference_title: "Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, we report an allelic series of germline recessive mutations in UGDH
      in 36 cases from 25 families presenting with epileptic encephalopathy with
      developmental delay and hypotonia.
    explanation: >-
      The cohort establishes UGDH as the causal gene for DEE84.