Congenital Phagocyte Defect IEIs (IUIS Table 5)

name: Congenital Phagocyte Defect IEIs
display_name: Congenital Phagocyte Defect IEIs (IUIS Table 5)
creation_date: "2026-08-20T00:00:00Z"
description: >-
  IUIS Table 5 — congenital defects of phagocyte number or function. These
  inborn errors of immunity impair the neutrophil/monocyte/macrophage
  compartment, either quantitatively (congenital neutropenia) or qualitatively
  (defective respiratory burst, adhesion, or chemotaxis). The characteristic
  clinical signature is recurrent deep bacterial and fungal infection —
  classically staphylococcal, Burkholderia, Nocardia, Serratia and Aspergillus
  — with abscess and granuloma formation rather than the viral and
  opportunistic susceptibility of T-cell disease.
grouping_basis:
- SHARED_MECHANISM
- SHARED_PHENOTYPE
grouping_rationale: >-
  Grouped on the IUIS Table 5 phagocyte-compartment lesion. Members are kept as
  separate Disease entries because the defect sits at a different point in
  phagocyte biology — CGD abolishes the NOX2 respiratory burst in a phagocyte
  that is present in normal numbers, whereas G6PC3 deficiency depletes the
  neutrophil itself through a metabolite-repair failure. Grouping them records
  that "phagocyte defect" is a compartment, not a mechanism: number and function
  are separate axes within the table and members may sit on either. No MONDO
  mapping: the Orphanet-derived grouping term for this table, MONDO:0015133
  (quantitative and/or qualitative congenital phagocyte defect), is obsolete,
  and MONDO:0005910 (phagocyte bactericidal dysfunction) covers only the
  functional axis, so it would silently exclude the neutropenia members.
membership_criteria:
- description: >-
    A disorder belongs to IUIS Table 5 if it is an inborn error of immunity
    whose primary lesion is in the number or the function of phagocytes
    (neutrophils, monocytes, macrophages, eosinophils).
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_CLASSIFICATION
    classification: "iuis_category:phagocyte defect"
    description: >-
      Assigned to IUIS Table 5 (congenital defects of phagocyte number or
      function) via classifications.iuis_category on the member Disease entry.
      Stated in the keyed `<slot>:<value>` form so the audit reads the
      structured classifications block.
members:
- member: Chronic Granulomatous Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Defects in the phagocyte NADPH oxidase (NOX2) complex abolish the
      respiratory burst, so phagocytes are present in normal numbers but cannot
      kill ingested catalase-positive bacteria and fungi. The functional axis of
      Table 5, and the member whose second phenotype — sterile granuloma and
      inflammatory bowel disease — comes from failed resolution of inflammation
      rather than from infection.
    gene:
      preferred_term: CYBB
      term:
        id: hgnc:2578
        label: CYBB
- member: G6PC3 Deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Biallelic G6PC3 loss is a metabolite-repair failure: unhydrolyzed
      1,5-anhydroglucitol-6-phosphate accumulates in granulocytes, inhibits
      hexokinase and stalls early glycolysis, causing neutrophil dysfunction and
      neutropenia. The quantitative axis of Table 5, and the member that shows a
      housekeeping enzymopathy reaching the immune system through a
      cell-type-specific metabolic vulnerability.
    gene:
      preferred_term: G6PC3
      term:
        id: hgnc:24861
        label: G6PC3
notes: >-
  Created 2026-08-20 to give the IUIS Table 5 disorders a place in the Inborn
  Errors of Immunity tree; both members already carried
  `classifications.iuis_category: phagocyte defect` but were unreachable from
  the umbrella grouping. Intentionally unmapped to MONDO — see
  grouping_rationale. Audit with
  `uv run python scripts/grouping_mondo_gaps.py --grouping "Inborn"`.