Inherited Porphyrias

name: Inherited Porphyrias
display_name: Inherited Porphyrias
creation_date: "2026-06-14T00:00:00Z"
description: >-
  A curated grouping of explicit inherited porphyria disease entries. Current
  members include the inherited porphyria umbrella entry plus acute intermittent
  porphyria and porphyria due to ALA dehydratase deficiency, representing the
  currently curated acute hepatic porphyria subtypes. Members share inherited
  heme-biosynthesis pathway disruption with porphyrin or porphyrin-precursor
  accumulation and variable neurovisceral, biochemical, hepatic, or cutaneous
  manifestations.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped as an explicit curated union of Disease entries for inherited
  porphyrias, not as all heme-pathway toxicities or all disorders with abnormal
  porphyrin biomarkers. Current standalone subtype coverage is concentrated in
  acute hepatic porphyrias, but the umbrella entry also documents additional
  hereditary hepatic, erythropoietic, and cutaneous porphyria subtypes. Future
  batches can add standalone hereditary coproporphyria, variegate porphyria,
  congenital erythropoietic porphyria, familial porphyria cutanea tarda,
  hepatoerythropoietic porphyria, and erythropoietic protoporphyria entries.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0019142
      label: inherited porphyria
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch: the grouping corresponds to the MONDO inherited porphyria
      class, but is implemented as an explicit curated subset of current
      dismech Disease entries rather than as an automatic MONDO closure over
      all hereditary porphyria subtypes.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        Listed members are the current KB inherited porphyria umbrella, acute
        intermittent porphyria, and porphyria due to ALA dehydratase deficiency
        entries. Additional inherited porphyria subtypes should be added when
        standalone Disease entries are curated.
membership_criteria:
- description: >-
    A member is an explicit inherited porphyria entry with heme-biosynthesis
    pathway disruption and at least one characteristic manifestation such as
    abdominal pain, peripheral neuropathy, abnormal circulating porphyrin
    concentration, or cutaneous photosensitivity.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    operands:
    - criterion_predicate: HAS_PHENOTYPE
      description: Abdominal pain.
      phenotype_term:
        preferred_term: Abdominal pain
        term:
          id: HP:0002027
          label: Abdominal pain
    - criterion_predicate: HAS_PHENOTYPE
      description: Peripheral neuropathy.
      phenotype_term:
        preferred_term: Peripheral neuropathy
        term:
          id: HP:0009830
          label: Peripheral neuropathy
    - criterion_predicate: HAS_PHENOTYPE
      description: Abnormal circulating porphyrin concentration.
      phenotype_term:
        preferred_term: Abnormal circulating porphyrin concentration
        term:
          id: HP:0010472
          label: Abnormal circulating porphyrin concentration
    - criterion_predicate: HAS_PHENOTYPE
      description: Cutaneous photosensitivity.
      phenotype_term:
        preferred_term: Cutaneous photosensitivity
        term:
          id: HP:0000992
          label: Cutaneous photosensitivity
members:
- member: Inherited Porphyria
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Umbrella inherited porphyria entry spanning hereditary defects in
      heme-biosynthesis enzymes or ALAS2 regulation, with hepatic or
      erythropoietic accumulation of ALA, PBG, porphyrins, or protoporphyrin and
      a clinical spectrum from acute neurovisceral attacks to photosensitivity,
      anemia, liver dysfunction, and chronic kidney disease.
- member: Acute Intermittent Porphyria
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Acute hepatic porphyria caused by HMBS deficiency, where hepatic ALAS1
      induction during triggers increases ALA and porphobilinogen production,
      causing acute neurovisceral attacks with abdominal pain, autonomic
      findings, hyponatremia, neuropathy, seizures, or psychiatric features.
    gene:
      preferred_term: HMBS
      term:
        id: hgnc:4982
        label: HMBS
- member: Porphyria due to ALA Dehydratase Deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Ultra-rare autosomal recessive acute hepatic porphyria caused by ALAD
      deficiency at the porphobilinogen synthase step, producing marked ALA
      accumulation with neurovisceral attacks, peripheral neuropathy, muscle
      weakness, abnormal porphyrin profiles, and no primary blistering skin
      phenotype.
    gene:
      preferred_term: ALAD
      term:
        id: hgnc:395
        label: ALAD
notes: >-
  Exclude acquired porphyria, lead poisoning, tyrosinemia type I, arsenic or
  toxin-related porphyrin abnormalities, AIP-related pituitary adenoma
  predisposition, and broad heme-biosynthesis or porphyrin-biomarker entries
  unless the standalone Disease entry is explicitly curated as an inherited
  porphyria subtype.