Disorders of Glyoxylate and Oxalate Metabolism

name: Disorders of Glyoxylate and Oxalate Metabolism
display_name: Disorders of Glyoxylate and Oxalate Metabolism
creation_date: "2026-07-06T06:09:44Z"
description: >-
  An auditable grouping of distinct DisMech disease entries whose primary
  defect disrupts glyoxylate, glycolate, oxalate, or calcium oxalate handling.
  Members include hepatic enzyme deficiencies that overproduce oxalate,
  HAO1/glycolate oxidase deficiency upstream of glyoxylate production, and
  transporter defects that alter oxalate handling and calcium oxalate stone
  risk.
grouping_basis:
- SHARED_PATHWAY
- SHARED_MECHANISM
grouping_rationale: >-
  The members are kept as separate Disease entries because their proximal
  mechanisms differ: AGXT and GRHPR are hepatic glyoxylate-metabolism enzyme
  defects with endogenous oxalate overproduction; HAO1 deficiency is a
  glycolate oxidase defect that primarily causes hyperglycolic aciduria; and
  SLC26A1/SLC26A6 are oxalate/anion transporter disorders. A grouping is useful
  because all five belong to the ICIMD glyoxylate-and-oxalate pathway bucket and
  share downstream concern for oxalate or calcium oxalate handling, while CAT
  catalase deficiency is intentionally excluded because it disrupts hydrogen
  peroxide metabolism instead.
membership_criteria:
- description: >-
    A member has a primary genetic defect in a glyoxylate/glycolate metabolic
    enzyme or an oxalate/anion transporter that materially changes oxalate,
    glycolate, glyoxylate, or calcium oxalate handling.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    operands:
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: AGXT
        term:
          id: hgnc:341
          label: AGXT
      description: AGXT/alanine-glyoxylate aminotransferase defect.
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: GRHPR
        term:
          id: hgnc:4570
          label: GRHPR
      description: GRHPR/glyoxylate reductase-hydroxypyruvate reductase defect.
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: HOGA1
        term:
          id: hgnc:25155
          label: HOGA1
      description: HOGA1/4-hydroxy-2-oxoglutarate aldolase defect.
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: HAO1
        term:
          id: hgnc:4809
          label: HAO1
      description: HAO1/glycolate oxidase defect.
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: SLC26A1
        term:
          id: hgnc:10993
          label: SLC26A1
      description: SLC26A1/SAT1 anion transporter defect.
    - criterion_predicate: HAS_GENE
      gene:
        preferred_term: SLC26A6
        term:
          id: hgnc:14472
          label: SLC26A6
      description: SLC26A6 epithelial oxalate transporter defect.
members:
- member: Primary Hyperoxaluria Type 1
  member_type: DISEASE
  disease_term:
    preferred_term: primary hyperoxaluria type 1
    term:
      id: MONDO:0009823
      label: primary hyperoxaluria type 1
  differentiating_mechanisms:
  - description: >-
      AGXT deficiency blocks hepatic peroxisomal glyoxylate-to-glycine
      transamination, diverting glyoxylate to oxalate and causing severe
      endogenous hyperoxaluria.
    gene:
      preferred_term: AGXT
      term:
        id: hgnc:341
        label: AGXT
    biological_processes:
    - preferred_term: glyoxylate metabolic process
      term:
        id: GO:0046487
        label: glyoxylate metabolic process
      modifier: DYSREGULATED
- member: Primary Hyperoxaluria Type 2
  member_type: DISEASE
  disease_term:
    preferred_term: primary hyperoxaluria type 2
    term:
      id: MONDO:0009824
      label: primary hyperoxaluria type 2
  differentiating_mechanisms:
  - description: >-
      GRHPR deficiency impairs glyoxylate-to-glycolate and
      hydroxypyruvate-to-D-glycerate flux, producing increased urinary oxalate
      and L-glycerate.
    gene:
      preferred_term: GRHPR
      term:
        id: hgnc:4570
        label: GRHPR
    biological_processes:
    - preferred_term: glyoxylate metabolic process
      term:
        id: GO:0046487
        label: glyoxylate metabolic process
      modifier: DYSREGULATED
- member: Primary Hyperoxaluria Type 3
  member_type: DISEASE
  disease_term:
    preferred_term: primary hyperoxaluria type 3
    term:
      id: MONDO:0013327
      label: primary hyperoxaluria type 3
  differentiating_mechanisms:
  - description: >-
      HOGA1 deficiency blocks the final mitochondrial step of hepatic
      hydroxyproline degradation (4-hydroxy-2-oxoglutarate aldolase), causing
      accumulation of 4-hydroxy-2-oxoglutarate and increased endogenous oxalate;
      PH3 is generally the mildest primary hyperoxaluria with rare progression
      to kidney failure.
    gene:
      preferred_term: HOGA1
      term:
        id: hgnc:25155
        label: HOGA1
    biological_processes:
    - preferred_term: glyoxylate metabolic process
      term:
        id: GO:0046487
        label: glyoxylate metabolic process
      modifier: DYSREGULATED
- member: HAO1-Related Glycolate Oxidase Deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      HAO1/glycolate oxidase deficiency reduces glycolate oxidation to
      glyoxylate, causing isolated hyperglycolic aciduria and generally benign
      biochemical disease rather than established recurrent calcium oxalate
      nephrolithiasis.
    gene:
      preferred_term: HAO1
      term:
        id: hgnc:4809
        label: HAO1
    biological_processes:
    - preferred_term: glyoxylate metabolic process
      term:
        id: GO:0046487
        label: glyoxylate metabolic process
      modifier: DECREASED
- member: SLC26A1-Related Oxalate Transporter Deficiency
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Biallelic SLC26A1/SAT1 variants reduce anion transporter activity and
      cause a recessive Mendelian calcium oxalate nephrolithiasis phenotype.
    gene:
      preferred_term: SLC26A1
      term:
        id: hgnc:10993
        label: SLC26A1
    biological_processes:
    - preferred_term: oxalate transport
      term:
        id: GO:0019532
        label: oxalate transport
      modifier: DECREASED
- member: SLC26A6-Related Hyperoxaluria and Nephrolithiasis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A rare dominant-negative SLC26A6 variant reduces epithelial oxalate
      transport, causing enteric hyperoxaluria and calcium oxalate
      nephrolithiasis in the reported family.
    gene:
      preferred_term: SLC26A6
      term:
        id: hgnc:14472
        label: SLC26A6
    biological_processes:
    - preferred_term: oxalate transport
      term:
        id: GO:0019532
        label: oxalate transport
      modifier: DECREASED
notes: >-
  Created for WP-032 to make the package boundary auditable without lumping
  distinct enzyme and transporter defects into one Disease entry.