Parkinsonism Dopaminergic Degeneration Disorders

Why this grouping

Grouped on the shared parkinsonism_dopaminergic_degeneration module: members share the parkinsonian motor-circuit endpoint while retaining different upstream causes. Parkinson's disease is a synucleinopathy with nigrostriatal dopaminergic neurodegeneration, mitochondrial dysfunction, and multiple genetic risk axes. Manganism is an acquired toxic basal-ganglia disorder from manganese accumulation and is deliberately kept separate because the exposure, anatomic emphasis, and treatment response differ from Parkinson's disease.

Membership criteria

NECESSARY AND SUFFICIENT (member ⇔ criteria)

A disorder belongs to this grouping if and only if it conforms to the parkinsonism dopaminergic degeneration module, linking dopaminergic or basal ganglia injury to striatal dopamine or circuit dysfunction and parkinsonism.

CONFORMS TO MODULE module: parkinsonism_dopaminergic_degeneration
Conforms to the parkinsonism dopaminergic degeneration module.

Coverage and gaps

5 rows Exact MONDO scope not assessed 2 listed with MONDO ID

No exact MONDO mapping is declared, so MONDO descendant gaps are not inferred for this grouping.

Status	DisMech entry	MONDO concept	In DisMech	Has MONDO ID	In grouping MONDO	Member state	Conditions satisfied	C1.1 Conforms to the parkinsonism dopaminergic degeneration module.
listed with MONDO ID	Parkinson's Disease DISEASE Differentiating mechanism Progressive synucleinopathy with alpha-synuclein aggregation, mitochondrial and lysosomal dysfunction, and nigrostriatal dopamine deficiency; genetic axes include SNCA, LRRK2, PRKN, PINK1, PARK7, VPS35, and GBA. SNCA hgnc:11138 inclusion body assembly GO:0070841	Parkinson disease MONDO:0005180	yes	yes	not assessed	listed	satisfied	SATISFIED
listed with MONDO ID	Manganism DISEASE Differentiating mechanism Acquired manganese poisoning with preferential basal-ganglia accumulation, oxidative stress, GABAergic circuit dysregulation, and parkinsonism that is exposure-driven rather than a primary synucleinopathy. response to oxidative stress GO:0006979	manganism MONDO:0017638	yes	yes	not assessed	listed	satisfied	SATISFIED
DisMech candidate	Autosomal Dominant Progressive External Ophthalmoplegia DISEASE	autosomal dominant progressive external ophthalmoplegia MONDO:0008003	yes	yes	not assessed	candidate	not evaluated	not evaluated
DisMech candidate	PARK7-Related Early-Onset Parkinson Disease DISEASE	autosomal recessive early-onset Parkinson disease 7 MONDO:0011658	yes	yes	not assessed	candidate	not evaluated	not evaluated
DisMech candidate	Neurodevelopmental Disorder with Early-Onset Parkinsonism and Behavioral Abnormalities DISEASE	neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities MONDO:0958323	yes	yes	not assessed	candidate	not evaluated	not evaluated

Source

View YAML on GitHub

Raw YAML

name: Parkinsonism Dopaminergic Degeneration Disorders
display_name: Parkinsonism Dopaminergic Degeneration Disorders
creation_date: "2026-06-18T00:00:00Z"
description: >-
  Parkinsonism dopaminergic degeneration disorders are entries that converge on
  basal ganglia motor circuit dysfunction with parkinsonism. Members may arise
  from neurodegenerative synucleinopathy or from environmental/toxic metal
  exposure, but both are represented through the
  parkinsonism_dopaminergic_degeneration module.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the shared parkinsonism_dopaminergic_degeneration module: members
  share the parkinsonian motor-circuit endpoint while retaining different
  upstream causes. Parkinson's disease is a synucleinopathy with nigrostriatal
  dopaminergic neurodegeneration, mitochondrial dysfunction, and multiple
  genetic risk axes. Manganism is an acquired toxic basal-ganglia disorder from
  manganese accumulation and is deliberately kept separate because the exposure,
  anatomic emphasis, and treatment response differ from Parkinson's disease.
membership_criteria:
- description: >-
    A disorder belongs to this grouping if and only if it conforms to the
    parkinsonism dopaminergic degeneration module, linking dopaminergic or basal
    ganglia injury to striatal dopamine or circuit dysfunction and parkinsonism.
  criteria_semantics: NECESSARY_AND_SUFFICIENT
  logic:
    criterion_predicate: CONFORMS_TO_MODULE
    module: parkinsonism_dopaminergic_degeneration
    description: >-
      Conforms to the parkinsonism dopaminergic degeneration module.
members:
- member: Manganism
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Acquired manganese poisoning with preferential basal-ganglia accumulation,
      oxidative stress, GABAergic circuit dysregulation, and parkinsonism that
      is exposure-driven rather than a primary synucleinopathy.
    biological_processes:
    - preferred_term: response to oxidative stress
      term:
        id: GO:0006979
        label: response to oxidative stress
      modifier: INCREASED
- member: Parkinson's Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Progressive synucleinopathy with alpha-synuclein aggregation, mitochondrial
      and lysosomal dysfunction, and nigrostriatal dopamine deficiency; genetic
      axes include SNCA, LRRK2, PRKN, PINK1, PARK7, VPS35, and GBA.
    gene:
      preferred_term: SNCA
      term:
        id: hgnc:11138
        label: SNCA
    biological_processes:
    - preferred_term: inclusion body assembly
      term:
        id: GO:0070841
        label: inclusion body assembly
      modifier: INCREASED
notes: >-
  Mixed mechanism/phenotype grouping over parkinsonian entries. It is distinct
  from the TDP-43 Proteinopathies grouping because its axis is dopaminergic and
  basal-ganglia motor-circuit dysfunction, not TDP-43 redistribution.