Thalassemias

name: Thalassemias
display_name: Thalassemias
creation_date: "2026-06-14T00:00:00Z"
description: >-
  A curated grouping of explicit thalassemia disease entries caused by
  inherited reduction or loss of alpha- or beta-globin chain synthesis. Members
  share globin-chain imbalance, abnormal hemoglobin biosynthesis, hypochromic
  microcytic anemia or reduced mean corpuscular volume, and variable chronic
  hemolysis, ineffective erythropoiesis, hepatosplenomegaly, iron overload, and
  skeletal marrow-expansion complications.
grouping_basis:
- SHARED_MECHANISM
- SHARED_GENE_FAMILY
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped as an explicit curated union of Disease entries whose primary
  disease identity is alpha- or beta-thalassemia, not as every hemoglobinopathy
  or every disorder with anemia. The shared boundary is inherited deficiency of
  globin-chain synthesis that creates alpha/beta-chain imbalance and downstream
  microcytic anemia with hemolytic or ineffective-erythropoiesis complications.
  Current members are the KB's standalone alpha and beta thalassemia entries;
  future batches can add separate Disease entries for clinically important
  subtype entities such as hemoglobin H disease, hemoglobin Bart hydrops fetalis
  syndrome, transfusion-dependent beta thalassemia, non-transfusion-dependent
  beta thalassemia, or compound hemoglobinopathy/thalassemia entities when those
  entries are curated independently.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0000984
      label: thalassemia
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch: the grouping corresponds to the MONDO thalassemia class but
      is implemented as an explicit curated subset of current dismech Disease
      entries rather than as an automatic ontology closure over every
      thalassemia subtype or compound hemoglobinopathy.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        The listed members map to MONDO alpha thalassemia spectrum and beta
        thalassemia entries. Additional MONDO thalassemia descendants should be
        added only when standalone Disease entries are curated.
membership_criteria:
- description: >-
    A member is an explicit alpha- or beta-thalassemia Disease entry with
    impaired hemoglobin biosynthesis and at least one core thalassemia
    hematologic phenotype, such as hypochromic microcytic anemia, decreased
    mean corpuscular volume, splenomegaly, or extramedullary hematopoiesis.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Involves decreased or abnormal hemoglobin biosynthesis.
      biological_processes:
      - preferred_term: hemoglobin biosynthetic process
        term:
          id: GO:0042541
          label: hemoglobin biosynthetic process
    - operator: OR
      description: Has a core thalassemia hematologic phenotype.
      operands:
      - criterion_predicate: HAS_PHENOTYPE
        description: Hypochromic microcytic anemia.
        phenotype_term:
          preferred_term: hypochromic microcytic anemia
          term:
            id: HP:0004840
            label: Hypochromic microcytic anemia
      - criterion_predicate: HAS_PHENOTYPE
        description: Decreased mean corpuscular volume.
        phenotype_term:
          preferred_term: decreased mean corpuscular volume
          term:
            id: HP:0025066
            label: Decreased mean corpuscular volume
      - criterion_predicate: HAS_PHENOTYPE
        description: Splenomegaly.
        phenotype_term:
          preferred_term: splenomegaly
          term:
            id: HP:0001744
            label: Splenomegaly
      - criterion_predicate: HAS_PHENOTYPE
        description: Extramedullary hematopoiesis.
        phenotype_term:
          preferred_term: extramedullary hematopoiesis
          term:
            id: HP:0001978
            label: Extramedullary hematopoiesis
members:
- member: Alpha Thalassemia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      HBA1/HBA2 deletions or inactivating variants reduce alpha-globin output,
      producing excess beta-globin tetramers in hemoglobin H disease or
      gamma-globin tetramers in hemoglobin Bart hydrops fetalis syndrome, with
      hemolysis, microcytosis, and severity determined by the number and type of
      affected alpha-globin alleles.
    gene:
      preferred_term: HBA1
      term:
        id: hgnc:4823
        label: HBA1
  - description: >-
      HBA2 variants are a second alpha-globin causal branch; because HBA2
      contributes more alpha-globin output than HBA1, non-deletional HBA2
      variants can produce disproportionately severe alpha-thalassemia
      phenotypes.
    gene:
      preferred_term: HBA2
      term:
        id: hgnc:4824
        label: HBA2
- member: Beta Thalassemia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      HBB beta-zero or beta-plus variants reduce or abolish beta-globin
      synthesis, leaving unpaired alpha-globin chains that precipitate in
      erythroid precursors and mature erythrocytes, causing ineffective
      erythropoiesis, chronic hemolysis, marrow expansion, splenomegaly, and
      iron-loading complications.
    gene:
      preferred_term: HBB
      term:
        id: hgnc:4827
        label: HBB
notes: >-
  Exclude ATRX/ATR-X syndrome and alpha-thalassemia X-linked intellectual
  disability unless a separate entry is being grouped specifically as an
  ATRX-related syndromic disorder; the alpha-thalassemia finding there is one
  component of a broader neurodevelopmental syndrome. Also exclude sickle cell
  disease, isolated HbE disease, malaria-protective carrier states, secondary
  iron overload, and anemia from non-globin causes unless the standalone Disease
  entry is explicitly curated as a thalassemia or thalassemia compound entity.