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.
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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
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.