Mucopolysaccharidoses (MPS)

name: Mucopolysaccharidoses
display_name: Mucopolysaccharidoses (MPS)
creation_date: "2026-06-12T00:00:00Z"
description: >-
  The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders
  caused by deficiency of the enzymes that catabolize glycosaminoglycans (GAGs,
  formerly mucopolysaccharides). Each MPS type results from a distinct enzyme
  deficiency, leading to progressive lysosomal accumulation of one or more GAG
  species (dermatan, heparan, keratan, or chondroitin sulfate) and a
  multisystem disease with overlapping skeletal, visceral, and—type
  dependent—neurological involvement.
grouping_basis:
- SHARED_MECHANISM
- SHARED_GENE_FAMILY
grouping_rationale: >-
  Grouped on a shared final-common-pathway mechanism: every member is caused by
  deficiency of a lysosomal GAG-degrading enzyme, producing lysosomal GAG
  storage (conforming to the lysosomal_substrate_accumulation module). The
  members are deliberately kept as separate Disease entries rather than merged,
  because they differ in the specific deficient enzyme and gene, the GAG
  species that accumulates, the mode of inheritance (MPS II / Hunter syndrome is
  X-linked, the others autosomal recessive), and the presence and severity of
  CNS involvement. This is therefore a grouping over distinct entities, not a
  lumping of them into one disease.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0019249
      label: mucopolysaccharidosis
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: >-
      The grouping concept corresponds to the MONDO mucopolysaccharidosis class.
      exactMatch records the intended conceptual alignment; MONDO MPS subtypes
      without DisMech entries are curation gaps rather than evidence that the
      grouping concept is only a close match.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        All 4 listed members are is-a descendants of MONDO:0019249. Additional
        MONDO MPS descendants without DisMech entries should be surfaced as
        curation gaps from this exact mapping.
membership_criteria:
- description: >-
    A disorder belongs to the mucopolysaccharidoses if it is a lysosomal
    storage disease of glycosaminoglycan catabolism: it conforms to the
    lysosomal substrate accumulation module AND is caused by deficiency of a
    GAG-degrading lysosomal enzyme AND presents with a characteristic
    connective-tissue GAG-storage manifestation (coarse facial features,
    dysostosis multiplex, or joint/periarticular storage disease — either
    structural, such as periarticular soft-tissue masses, or restrictive, such
    as joint stiffness and contracture).
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: CONFORMS_TO_MODULE
      module: lysosomal_substrate_accumulation#Lysosomal Substrate Accumulation
      description: >-
        Has a pathophysiology node conforming to the lysosomal substrate
        accumulation module (lysosomal GAG storage).
    - criterion_predicate: HAS_BIOLOGICAL_PROCESS
      description: Deficient catabolism of glycosaminoglycans.
      biological_processes:
      - preferred_term: Glycosaminoglycan catabolic process
        term:
          id: GO:0006027
          label: glycosaminoglycan catabolic process
        modifier: DECREASED
    - operator: OR
      description: >-
        At least one hallmark connective-tissue GAG-storage manifestation is
        present. The joint operand is not decoration: MPS IX (Natowicz
        syndrome) stores hyaluronan rather than a sulfated GAG and has neither
        coarse facies nor dysostosis multiplex, presenting instead with
        periarticular soft-tissue masses, so a criterion admitting only the two
        classic hallmarks would contradict its curated membership.
      operands:
      - criterion_predicate: HAS_PHENOTYPE
        description: Coarse facial features in many or most cases.
        phenotype_term:
          preferred_term: Coarse facial features
          term:
            id: HP:0000280
            label: Coarse facial features
        min_frequency: FREQUENT
      - criterion_predicate: HAS_PHENOTYPE
        description: Dysostosis multiplex.
        phenotype_term:
          preferred_term: Dysostosis multiplex
          term:
            id: HP:0000943
            label: Dysostosis multiplex
      - criterion_predicate: HAS_PHENOTYPE
        description: >-
          Structural joint or periarticular storage manifestation (joint
          swelling or periarticular soft-tissue mass). Kept separate from the
          mobility operand below because HP splits joint structure from joint
          function, and the two MPS joint phenotypes fall on opposite sides of
          that split.
        phenotype_term:
          preferred_term: Abnormal joint morphology
          term:
            id: HP:0001367
            label: Abnormal joint morphology
      - criterion_predicate: HAS_PHENOTYPE
        description: >-
          Joint mobility restriction from periarticular GAG storage (joint
          stiffness or contracture) — the near-universal MPS joint phenotype.
        phenotype_term:
          preferred_term: Abnormality of joint mobility
          term:
            id: HP:0011729
            label: Abnormality of joint mobility
members:
- member: Hurler syndrome
  member_type: DISEASE
  display_name: Hurler syndrome (MPS I)
  differentiating_mechanisms:
  - description: >-
      Autosomal recessive deficiency of alpha-L-iduronidase (IDUA), causing
      lysosomal accumulation of dermatan sulfate and heparan sulfate; the severe
      end of the MPS I spectrum, with prominent neurodegeneration.
    gene:
      preferred_term: IDUA
      term:
        id: hgnc:5391
        label: IDUA
- member: Hunter syndrome
  member_type: DISEASE
  display_name: Hunter syndrome (MPS II)
  differentiating_mechanisms:
  - description: >-
      X-linked deficiency of iduronate-2-sulfatase (IDS)—the only X-linked
      MPS—causing accumulation of dermatan and heparan sulfate. Absence of
      corneal clouding helps distinguish it clinically from MPS I.
    gene:
      preferred_term: IDS
      term:
        id: hgnc:5389
        label: IDS
- member: Sanfilippo syndrome
  member_type: DISEASE
  display_name: Sanfilippo syndrome (MPS III)
  differentiating_mechanisms:
  - description: >-
      Deficiency of one of several enzymes of heparan sulfate degradation
      (e.g., SGSH in MPS IIIA), causing selective heparan sulfate accumulation.
      Distinguished by severe, early progressive CNS degeneration with
      comparatively mild somatic/skeletal disease.
    gene:
      preferred_term: SGSH
      term:
        id: hgnc:10818
        label: SGSH
- member: Morquio syndrome
  member_type: DISEASE
  display_name: Morquio syndrome (MPS IV)
  differentiating_mechanisms:
  - description: >-
      Deficiency of N-acetylgalactosamine-6-sulfatase (GALNS, MPS IVA) causing
      keratan and chondroitin-6-sulfate accumulation. Distinguished by a
      predominantly skeletal phenotype (spondyloepiphyseal dysplasia,
      odontoid hypoplasia) with preserved intelligence.
    gene:
      preferred_term: GALNS
      term:
        id: hgnc:4122
        label: GALNS
- member: Maroteaux-Lamy syndrome
  member_type: DISEASE
  display_name: Maroteaux-Lamy syndrome (MPS VI)
  differentiating_mechanisms:
  - description: >-
      Autosomal recessive deficiency of N-acetylgalactosamine-4-sulfatase
      (arylsulfatase B, ARSB) causing selective dermatan sulfate accumulation.
      Distinguished by severe somatic and skeletal disease — dysostosis
      multiplex, valvular heart disease, corneal clouding — with intelligence
      characteristically preserved, because heparan sulfate (the CNS-toxic GAG
      of MPS I/II/III) is not a substrate of ARSB.
    gene:
      preferred_term: ARSB
      term:
        id: hgnc:714
        label: ARSB
- member: Sly syndrome
  member_type: DISEASE
  display_name: Sly syndrome (MPS VII)
  differentiating_mechanisms:
  - description: >-
      Deficiency of beta-glucuronidase (GUSB), the exoglycosidase acting on
      dermatan, heparan, and chondroitin sulfate, so all three GAG species
      accumulate. Distinguished by the highest frequency of presentation as
      non-immune hydrops fetalis among the MPS disorders, alongside a variable
      postnatal spectrum with CNS involvement.
    gene:
      preferred_term: GUSB
      term:
        id: hgnc:4696
        label: GUSB
- member: Mucopolysaccharidosis type IX
  member_type: DISEASE
  display_name: Mucopolysaccharidosis type IX (Natowicz syndrome)
  differentiating_mechanisms:
  - description: >-
      Deficiency of lysosomal hyaluronidase 1 (HYAL1) causing hyaluronan — not
      a sulfated GAG — to accumulate. The mechanistic outlier of the group: an
      ultra-rare, essentially non-neuronopathic disorder of periarticular soft
      tissue masses and short stature, without the coarse facies or classic
      dysostosis multiplex that the other MPS types share.
    gene:
      preferred_term: HYAL1
      term:
        id: hgnc:5320
        label: HYAL1
notes: >-
  Worked example of the Grouping schema. Members reference existing Disease
  entries by name; differentiating mechanisms cite the disorder-specific
  deficient enzyme/gene. CNS involvement and GAG species differ across types.