Single Large-Scale mtDNA Deletion Disorders

name: Single Large-Scale mtDNA Deletion Disorders
display_name: Single Large-Scale mtDNA Deletion Disorders
creation_date: "2026-07-06T01:07:38Z"
description: >-
  A grouping for disorders caused by a single large-scale mitochondrial DNA
  deletion. Members share a primary heteroplasmic mtDNA deletion that impairs
  mitochondrial translation and oxidative phosphorylation, but they remain
  separate disease entries because deleted-mtDNA tissue distribution, timing,
  and dominant organ vulnerability produce distinct clinical syndromes.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PATHWAY
- CLINICAL_CONVENTION
grouping_rationale: >-
  Pearson syndrome and Kearns-Sayre syndrome are kept split because each has a
  distinct MONDO/OMIM/Orphanet identity and a different dominant tissue
  phenotype: Pearson syndrome is an infantile marrow-pancreas/multisystem
  presentation with high early hematologic burden, whereas Kearns-Sayre syndrome
  is a childhood-onset post-mitotic ocular-retinal-cardiac syndrome. They are
  grouped here because the upstream causal event is the same class of lesion,
  a single large-scale mtDNA deletion, and both entries converge on impaired
  mitochondrial translation, oxidative phosphorylation, lactate accumulation,
  and high-energy tissue dysfunction. This grouping is an auditable union of
  the curated WP-015 seeds and is not intended to exhaust all SLSMD phenotypes
  such as isolated CPEO or CPEO-plus.
membership_criteria:
- description: >-
    A listed member has a disease-causing single large-scale mtDNA deletion and
    explicitly models mitochondrial DNA disruption with downstream
    mitochondrial dysfunction / oxidative phosphorylation failure.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: The entry models disruption of mitochondrial DNA biology.
      biological_processes:
      - preferred_term: mitochondrial DNA metabolic process
        term:
          id: GO:0032042
          label: mitochondrial DNA metabolic process
        modifier: ABNORMAL
    - criterion_predicate: CONFORMS_TO_MODULE
      module: mitochondrial_dysfunction#Bioenergetic Decline and Oxidative Stress
      description: >-
        The entry specializes the mitochondrial dysfunction bioenergetic-decline
        node for the disease-specific tissue context.
members:
- member: Pearson syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Infantile high-burden deleted mtDNA in hematopoietic and exocrine
      pancreatic contexts produces transfusion-dependent sideroblastic anemia,
      pancytopenia with marrow precursor vacuolization, exocrine pancreatic
      dysfunction, poor growth, renal tubular disease, and lactic acidosis.
    biological_processes:
    - preferred_term: mitochondrial DNA metabolic process
      term:
        id: GO:0032042
        label: mitochondrial DNA metabolic process
      modifier: ABNORMAL
    phenotype_term:
      preferred_term: Sideroblastic anemia
      term:
        id: HP:0001924
        label: Sideroblastic anemia
    module: mitochondrial_dysfunction#Bioenergetic Decline and Oxidative Stress
- member: Kearns-Sayre syndrome
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Deleted mtDNA in post-mitotic tissues produces the ocular-retinal-cardiac
      syndrome of chronic progressive external ophthalmoplegia, pigmentary
      retinopathy, and cardiac conduction block, with neurologic and endocrine
      complications in many patients.
    biological_processes:
    - preferred_term: mitochondrial DNA metabolic process
      term:
        id: GO:0032042
        label: mitochondrial DNA metabolic process
      modifier: ABNORMAL
    phenotype_term:
      preferred_term: Progressive external ophthalmoplegia
      term:
        id: HP:0000590
        label: Progressive external ophthalmoplegia
    module: mitochondrial_dysfunction#Bioenergetic Decline and Oxidative Stress
notes: >-
  Curation scope: WP-015 only assigned Pearson syndrome and Kearns-Sayre
  syndrome. Isolated CPEO, CPEO-plus, and other atypical SLSMD presentations are
  intentionally noted as future curation candidates rather than silently added
  without seed assignment.