Glycoproteinoses (oligosaccharidoses)

name: Glycoproteinoses
display_name: Glycoproteinoses (oligosaccharidoses)
creation_date: "2026-10-11T00:00:00Z"
description: >-
  The glycoproteinoses (oligosaccharidoses, glycoprotein storage diseases) are
  autosomal recessive lysosomal storage disorders in which a defect in the
  stepwise lysosomal degradation of the N- and O-linked glycans of
  glycoproteins causes accumulation of undegraded oligosaccharides and
  glycopeptides, with urinary oligosaccharide or glycopeptide excretion and a
  progressive multisystem, often neurodegenerative, phenotype. Each member is
  caused by deficiency of a different lysosomal glycosidase or amidase, or, in
  galactosialidosis, of the protective protein that stabilizes two of them.
grouping_basis:
- SHARED_MECHANISM
- CLINICAL_CONVENTION
grouping_rationale: >-
  Grouped on a shared mechanism: every member is a failure of lysosomal
  glycoprotein glycan catabolism, producing oligosaccharide/glycopeptide
  storage. The members are kept as separate Disease entries because they differ
  in the deficient enzyme and gene, the stored glycan species, and the clinical
  course (for example the immune phenotype of alpha-mannosidosis, the
  normosomatic myoclonus form of sialidosis type 1, the angiokeratoma of
  Kanzaki disease). The class-level Disease entry Glycoprotein_Storage_Disease
  (MONDO:0009296) models the shared final common pathway and is deliberately
  not listed as a member, because it is the class itself rather than one of the
  diseases it contains; this grouping is the explicit member union that entry
  describes in prose.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0009296
      label: glycoprotein storage disease
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      The grouping concept corresponds to the MONDO glycoprotein storage disease
      class. closeMatch rather than exactMatch because the Disease entry
      Glycoprotein_Storage_Disease already carries MONDO:0009296 as its exact
      disease_term, and the member list here (which includes galactosialidosis
      and the three NAGA deficiency forms) has not been audited against MONDO's
      descendant closure.
membership_criteria:
- description: >-
    A disorder belongs to the glycoproteinoses only if its causal gene encodes a
    lysosomal enzyme of glycoprotein glycan degradation (FUCA1, MAN2B1, MANBA,
    AGA, NEU1, NAGA) or the protective protein CTSA that stabilizes NEU1 and
    beta-galactosidase in the lysosome.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    description: The causal locus is one of the glycoproteinosis genes.
    operands:
    - criterion_predicate: HAS_GENE
      description: Deficiency of lysosomal alpha-L-fucosidase (FUCA1).
      gene:
        preferred_term: FUCA1
        term:
          id: hgnc:4006
          label: FUCA1
    - criterion_predicate: HAS_GENE
      description: Deficiency of lysosomal alpha-mannosidase (MAN2B1).
      gene:
        preferred_term: MAN2B1
        term:
          id: hgnc:6826
          label: MAN2B1
    - criterion_predicate: HAS_GENE
      description: Deficiency of lysosomal beta-mannosidase (MANBA).
      gene:
        preferred_term: MANBA
        term:
          id: hgnc:6831
          label: MANBA
    - criterion_predicate: HAS_GENE
      description: Deficiency of aspartylglucosaminidase (AGA).
      gene:
        preferred_term: AGA
        term:
          id: hgnc:318
          label: AGA
    - criterion_predicate: HAS_GENE
      description: Deficiency of lysosomal neuraminidase 1 (NEU1).
      gene:
        preferred_term: NEU1
        term:
          id: hgnc:7758
          label: NEU1
    - criterion_predicate: HAS_GENE
      description: Deficiency of protective protein/cathepsin A (CTSA), with secondary loss of NEU1 and beta-galactosidase.
      gene:
        preferred_term: CTSA
        term:
          id: hgnc:9251
          label: CTSA
    - criterion_predicate: HAS_GENE
      description: Deficiency of alpha-N-acetylgalactosaminidase (NAGA).
      gene:
        preferred_term: NAGA
        term:
          id: hgnc:7631
          label: NAGA
members:
- member: Fucosidosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Alpha-L-fucosidase (FUCA1) deficiency stores fucose-containing glycoproteins, glycolipids and oligosaccharides; progressive neurodegeneration with angiokeratoma in longer-surviving patients.
    gene:
      preferred_term: FUCA1
      term:
        id: hgnc:4006
        label: FUCA1
- member: Alpha-mannosidosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Lysosomal alpha-mannosidase (MAN2B1) deficiency stores mannose-rich oligosaccharides; intellectual disability, hearing loss and immunodeficiency with recurrent infection are distinguishing.
    gene:
      preferred_term: MAN2B1
      term:
        id: hgnc:6826
        label: MAN2B1
- member: Beta Mannosidosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Lysosomal beta-mannosidase (MANBA) deficiency blocks removal of the core beta-linked mannose, storing a disaccharide; usually a milder, variable phenotype dominated by intellectual disability and hearing loss.
    gene:
      preferred_term: MANBA
      term:
        id: hgnc:6831
        label: MANBA
- member: Aspartylglucosaminuria
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Aspartylglucosaminidase (AGA) deficiency blocks cleavage of the asparagine-GlcNAc linkage, the final step of N-glycoprotein degradation, storing aspartylglucosamine; slowly progressive intellectual decline, Finnish-enriched.
    gene:
      preferred_term: AGA
      term:
        id: hgnc:318
        label: AGA
- member: Sialidosis type 1
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Partial neuraminidase 1 (NEU1) deficiency stores sialyloligosaccharides in the normosomatic, later-onset cherry-red spot myoclonus form, without dysmorphism or dysostosis.
    gene:
      preferred_term: NEU1
      term:
        id: hgnc:7758
        label: NEU1
- member: Juvenile Sialidosis Type 2
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      NEU1 deficiency in the childhood-onset dysmorphic (type 2) form, with coarse facies, dysostosis multiplex and progressive neurological impairment.
    gene:
      preferred_term: NEU1
      term:
        id: hgnc:7758
        label: NEU1
- member: Congenital Sialidosis Type 2
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Profound NEU1 deficiency in the congenital (type 2) form, presenting with nonimmune hydrops fetalis or neonatal ascites.
    gene:
      preferred_term: NEU1
      term:
        id: hgnc:7758
        label: NEU1
- member: Galactosialidosis
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Loss of the protective protein/cathepsin A (CTSA) destabilizes the lysosomal multienzyme complex, causing combined secondary deficiency of NEU1 and beta-galactosidase; sialidosis-like storage with a protein-stabilization rather than glycosidase-gene lesion.
    gene:
      preferred_term: CTSA
      term:
        id: hgnc:9251
        label: CTSA
- member: Schindler Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Alpha-N-acetylgalactosaminidase (NAGA) deficiency in its severe infantile neuroaxonal dystrophy form (type 1).
    gene:
      preferred_term: NAGA
      term:
        id: hgnc:7631
        label: NAGA
- member: Kanzaki Disease
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      NAGA deficiency in the adult-onset form (type 2) with angiokeratoma corporis diffusum and milder neurological involvement.
    gene:
      preferred_term: NAGA
      term:
        id: hgnc:7631
        label: NAGA
- member: NAGA Deficiency Type 3
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      NAGA deficiency in the intermediate form (type 3), with variable neurological and psychiatric presentation.
    gene:
      preferred_term: NAGA
      term:
        id: hgnc:7631
        label: NAGA
notes: >-
  Created as the explicit member union for the class-level Disease entry
  Glycoprotein_Storage_Disease, which names these member disorders in its
  description. Nine of the eleven members are also listed directly in
  Lysosomal_Storage_Disorders; Fucosidosis and Beta Mannosidosis are not.
  Nesting this grouping inside Lysosomal_Storage_Disorders (replacing its
  direct oligosaccharidosis rows) is a decision for that grouping and has not
  been made here.