Manganism

Neurological Disorder MONDO:0017638 Pathograph 2 Show in embeddings browser Secondary Parkinsonism Environmental Neurotoxicity

Manganism is an acquired, environmentally caused extrapyramidal movement disorder produced by chronic excessive exposure to manganese (Mn), classically occupational (welding, mining, ferroalloy and battery manufacture, and contaminated water or total parenteral nutrition). Inhaled or ingested manganese accumulates preferentially in the basal ganglia — initially the globus pallidus — producing a parkinsonism-like syndrome with bradykinesia, rigidity, dystonia (the characteristic "cock-walk"), gait disturbance, and neuropsychiatric features. Manganism is clinically and pathophysiologically distinct from idiopathic Parkinson disease: the lesion is predominantly pallidal rather than nigrostriatal, and it characteristically responds poorly to levodopa. It is a paradigm environmental-neurotoxicity cause of secondary parkinsonism and converges on basal-ganglia motor-circuit dysfunction.

Ask OpenScientist

Ask a research question about Manganism. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

2
Pathophys.
1
Phenotypes
2
Pathograph
2
Datasets
⚙

Pathophysiology

2
Chronic Manganese Accumulation in the Basal Ganglia
Chronic inhalational or ingested manganese crosses into the CNS and accumulates preferentially in the basal ganglia, initially the globus pallidus and, with prolonged lower-level exposure, extending across the basal ganglia toward the substantia nigra pars compacta. This metal deposition (visible as T1 MRI hyperintensity) and the attendant oxidative stress are the initiating lesion of the disorder.
response to oxidative stress GO:0006979 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased response to oxidative stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology. ↑ INCREASED
basal ganglia UBERON:0002420 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in basal ganglia, annotated with basal ganglion (UBERON:0002420). UBERON:0002420 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Basal Ganglia Circuit Dysfunction and Extrapyramidal Parkinsonism Manganese accumulation in the globus pallidus disrupts basal ganglia output circuitry.
Show evidence (2 references)
PMID:20012385 SUPPORT Other
"Such chronic exposures may progressively extend the site of manganese deposition and toxicity from the globus pallidus to the entire area of the basal ganglia, including the substantia nigra pars compacta involved in Parkinson's disease."
Describes the conserved deposition pattern — pallidal first, then wider basal ganglia and substantia nigra — that defines the anatomic lesion of manganism.
PMID:37627255 SUPPORT Other
"the target areas extend beyond the globus pallidus (as seen with manganism) to the entire basal ganglia, including the substantia nigra pars compacta."
Independent review corroborates the basal ganglia/substantia nigra target distribution of chronic manganese exposure.
Basal Ganglia Circuit Dysfunction and Extrapyramidal Parkinsonism
Manganese accumulation in the globus pallidus perturbs the basal ganglia-thalamocortical motor circuit, influencing the subthalamic nucleus and substantia nigra and thereby altering thalamic and cortical motor output. The result is an extrapyramidal, parkinsonism-like syndrome. This node is a partial conformer to the parkinsonism dopaminergic-degeneration module: it converges on basal-ganglia motor-circuit dysfunction and parkinsonism but, unlike idiopathic Parkinson disease, the predominant lesion is pallidal rather than nigrostriatal-dopaminergic, accounting for the characteristically poor levodopa response.
GABAergic neuron CL:0000617 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves GABAergic neuron (CL:0000617). CL:0000617 is a cell type from the Cell Ontology.
GABAergic synaptic transmission GO:0051932 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated GABAergic synaptic transmission, annotated with synaptic transmission, GABAergic (GO:0051932). GO:0051932 is a biological process from the Gene Ontology. ↕ DYSREGULATED
basal ganglia UBERON:0002420 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in basal ganglia, annotated with basal ganglion (UBERON:0002420). UBERON:0002420 is an anatomical location from the Uberon multi-species anatomy ontology.
Show evidence (2 references)
PMID:26608821 SUPPORT Other
"when accumulated in the globus pallidus, Mn influences the subthalamic (STN) and substantia nigra (SN) neurons, which are at the origin of changes in the thalamus and the cortex."
Mechanistically links pallidal manganese accumulation to disrupted basal ganglia-thalamocortical output, the circuit basis of the parkinsonian phenotype and the conformance to the module's basal-ganglia node.
PMID:20012385 SUPPORT Other
"Manganism is a distinct medical condition from Parkinson's disease."
Supports the entry's explicit distinction between manganism and idiopathic Parkinson disease, the basis for treating this as a partial (pallidal, levodopa-poor) conformer rather than a full nigrostriatal one.
⬡

Pathograph

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

1
Extrapyramidal Parkinsonism HP:0001300 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Parkinsonism (HP:0001300). HP:0001300 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:26608821 SUPPORT Other
"Manganism is an extrapyramidal disorder characterized by motor disturbances associated with neuropsychiatric and cognitive disabilities similar to Parkinsonism."
Establishes the parkinsonism-like extrapyramidal motor phenotype that defines the disorder clinically.
🌍

Environmental Factors

1
Occupational and Environmental Manganese Exposure
manganese exposure ECTO:9000946 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is manganese exposure, annotated with exposure to manganese (ECTO:9000946). ECTO:9000946 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Manganism results from chronic excessive manganese exposure. Historically this was acute high-level occupational inhalation (mining, ore processing); contemporary exposure is more often chronic lower-level inhalation (welding, ferroalloy and battery manufacture) or ingestion (contaminated drinking water, total parenteral nutrition, or impaired hepatobiliary manganese excretion).
Show evidence (1 reference)
PMID:20012385 SUPPORT Other
"Manganese exposure scenarios in the last century generally have changed from the acute, high-level exposure conditions responsible for the occurrence of manganism to chronic exposure to much lower levels."
Documents the shift in occupational/environmental manganese exposure that defines the modern epidemiology of manganism.
📊

Related Datasets

2
Small noncoding RNA Dysregulation is Implicated in Manganism in a Rat Model of Methylcyclopentadienyl Manganese Tricarbonyl-Induced Unrepaired Striatum Damage geo:GSE227299
Excessive accumulation of manganese in brain can cause Parkinsonian-like symptoms, known as Manganism. Methylcyclopentadienyl Manganese Tricarbonyl (MMT), a gasoline antiknock additive, is one of environmental exposures of manganese, which can lead to manganism in Rats. Though some researches showed that small non-coding RNAs (sncRNAs) were differently expressed in Parkinson’s disease (PD) patients, it was still unclear whether and how sncRNAs dysfunction appeared in Manganism.
rat BULK RNA SEQ n=9
Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
A humanized neuronal model system reveals key roles for the trace element manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics geo:GSE266943
Manganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinson’s and Alzheimer’s disease. Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood.
human BULK RNA SEQ n=48
PMID:40917882
Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
{ }

Source YAML

click to show 
name: Manganism
creation_date: "2026-06-11T00:00:00Z"
category: Neurological Disorder
parents:
- Secondary Parkinsonism
- Environmental Neurotoxicity
disease_term:
  preferred_term: manganism
  term:
    id: MONDO:0017638
    label: manganese poisoning
description: >-
  Manganism is an acquired, environmentally caused extrapyramidal movement
  disorder produced by chronic excessive exposure to manganese (Mn), classically
  occupational (welding, mining, ferroalloy and battery manufacture, and
  contaminated water or total parenteral nutrition). Inhaled or ingested
  manganese accumulates preferentially in the basal ganglia — initially the
  globus pallidus — producing a parkinsonism-like syndrome with bradykinesia,
  rigidity, dystonia (the characteristic "cock-walk"), gait disturbance, and
  neuropsychiatric features. Manganism is clinically and pathophysiologically
  distinct from idiopathic Parkinson disease: the lesion is predominantly
  pallidal rather than nigrostriatal, and it characteristically responds poorly
  to levodopa. It is a paradigm environmental-neurotoxicity cause of secondary
  parkinsonism and converges on basal-ganglia motor-circuit dysfunction.
pathophysiology:
- name: Chronic Manganese Accumulation in the Basal Ganglia
  description: >-
    Chronic inhalational or ingested manganese crosses into the CNS and
    accumulates preferentially in the basal ganglia, initially the globus
    pallidus and, with prolonged lower-level exposure, extending across the basal
    ganglia toward the substantia nigra pars compacta. This metal deposition
    (visible as T1 MRI hyperintensity) and the attendant oxidative stress are the
    initiating lesion of the disorder.
  role: trigger
  locations:
  - preferred_term: basal ganglia
    term:
      id: UBERON:0002420
      label: basal ganglion
  biological_processes:
  - preferred_term: response to oxidative stress
    term:
      id: GO:0006979
      label: response to oxidative stress
    modifier: INCREASED
  evidence:
  - reference: PMID:20012385
    reference_title: "From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Such chronic exposures may progressively extend the site of manganese
      deposition and toxicity from the globus pallidus to the entire area of the
      basal ganglia, including the substantia nigra pars compacta involved in
      Parkinson's disease.
    explanation: >-
      Describes the conserved deposition pattern — pallidal first, then wider
      basal ganglia and substantia nigra — that defines the anatomic lesion of
      manganism.
  - reference: PMID:37627255
    reference_title: "Manganese-Induced Parkinsonism: Evidence from Epidemiological and Experimental Studies."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      the target areas extend beyond the globus pallidus (as seen with
      manganism) to the entire basal ganglia, including the substantia nigra pars
      compacta.
    explanation: >-
      Independent review corroborates the basal ganglia/substantia nigra target
      distribution of chronic manganese exposure.
  downstream:
  - target: Basal Ganglia Circuit Dysfunction and Extrapyramidal Parkinsonism
    description: >-
      Manganese accumulation in the globus pallidus disrupts basal ganglia output
      circuitry.
- name: Basal Ganglia Circuit Dysfunction and Extrapyramidal Parkinsonism
  conforms_to: "parkinsonism_dopaminergic_degeneration#Striatal Dopamine Deficiency and Basal Ganglia Circuit Dysfunction"
  description: >-
    Manganese accumulation in the globus pallidus perturbs the basal
    ganglia-thalamocortical motor circuit, influencing the subthalamic nucleus
    and substantia nigra and thereby altering thalamic and cortical motor output.
    The result is an extrapyramidal, parkinsonism-like syndrome. This node is a
    partial conformer to the parkinsonism dopaminergic-degeneration module: it
    converges on basal-ganglia motor-circuit dysfunction and parkinsonism but,
    unlike idiopathic Parkinson disease, the predominant lesion is pallidal
    rather than nigrostriatal-dopaminergic, accounting for the characteristically
    poor levodopa response.
  role: effector
  cell_types:
  - preferred_term: GABAergic neuron
    term:
      id: CL:0000617
      label: GABAergic neuron
  biological_processes:
  - preferred_term: GABAergic synaptic transmission
    term:
      id: GO:0051932
      label: synaptic transmission, GABAergic
    modifier: DYSREGULATED
  locations:
  - preferred_term: basal ganglia
    term:
      id: UBERON:0002420
      label: basal ganglion
  evidence:
  - reference: PMID:26608821
    reference_title: "Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      when accumulated in the globus pallidus, Mn influences the subthalamic
      (STN) and substantia nigra (SN) neurons, which are at the origin of changes
      in the thalamus and the cortex.
    explanation: >-
      Mechanistically links pallidal manganese accumulation to disrupted basal
      ganglia-thalamocortical output, the circuit basis of the parkinsonian
      phenotype and the conformance to the module's basal-ganglia node.
  - reference: PMID:20012385
    reference_title: "From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Manganism is a distinct medical condition from Parkinson's disease.
    explanation: >-
      Supports the entry's explicit distinction between manganism and idiopathic
      Parkinson disease, the basis for treating this as a partial (pallidal,
      levodopa-poor) conformer rather than a full nigrostriatal one.
environmental:
- name: Occupational and Environmental Manganese Exposure
  exposure_term:
    preferred_term: manganese exposure
    term:
      id: ECTO:9000946
      label: exposure to manganese
  notes: >-
    Manganism results from chronic excessive manganese exposure. Historically
    this was acute high-level occupational inhalation (mining, ore processing);
    contemporary exposure is more often chronic lower-level inhalation (welding,
    ferroalloy and battery manufacture) or ingestion (contaminated drinking
    water, total parenteral nutrition, or impaired hepatobiliary manganese
    excretion).
  evidence:
  - reference: PMID:20012385
    reference_title: "From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Manganese exposure scenarios in the last century generally have changed
      from the acute, high-level exposure conditions responsible for the
      occurrence of manganism to chronic exposure to much lower levels.
    explanation: >-
      Documents the shift in occupational/environmental manganese exposure that
      defines the modern epidemiology of manganism.
phenotypes:
- name: Extrapyramidal Parkinsonism
  phenotype_term:
    preferred_term: Parkinsonism
    term:
      id: HP:0001300
      label: Parkinsonism
  evidence:
  - reference: PMID:26608821
    reference_title: "Manganese neurotoxicity: behavioral disorders associated with dysfunctions in the basal ganglia and neurochemical transmission."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Manganism is an extrapyramidal disorder characterized by motor disturbances
      associated with neuropsychiatric and cognitive disabilities similar to
      Parkinsonism.
    explanation: >-
      Establishes the parkinsonism-like extrapyramidal motor phenotype that
      defines the disorder clinically.
datasets:
- accession: geo:GSE227299
  title: Small noncoding RNA Dysregulation is Implicated in Manganism in a Rat Model of Methylcyclopentadienyl Manganese Tricarbonyl-Induced Unrepaired Striatum Damage
  description: Excessive accumulation of manganese in brain can cause Parkinsonian-like symptoms, known as Manganism. Methylcyclopentadienyl Manganese Tricarbonyl (MMT), a gasoline antiknock additive, is one of environmental exposures of manganese, which can lead to manganism in Rats. Though some researches showed that small non-coding RNAs (sncRNAs) were differently expressed in Parkinson’s disease (PD) patients, it was still unclear whether and how sncRNAs dysfunction appeared in Manganism.
  organism:
    preferred_term: rat
    term:
      id: NCBITaxon:10116
      label: Rattus norvegicus
  data_type: BULK_RNA_SEQ
  sample_count: 9
  notes: Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE266943
  title: A humanized neuronal model system reveals key roles for the trace element manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics
  description: Manganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinson’s and Alzheimer’s disease. Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 48
  publication: PMID:40917882
  notes: Identified by GEO DataSets index search for Manganism (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.