Maroteaux-Lamy syndrome

Mendelian MONDO:0009661 Pathograph 17 Show in embeddings browser Mucopolysaccharidosis Lysosomal Storage Disorder

Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS VI), is an autosomal recessive lysosomal storage disorder caused by deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ARSB). ARSB deficiency blocks lysosomal degradation of dermatan sulfate, leading to intracellular and extracellular accumulation of undegraded dermatan sulfate (with chondroitin-4-sulfate) in connective-tissue fibroblasts and the extracellular matrix of bone, cartilage, heart valve, cornea, and viscera. Because dermatan sulfate is the only stored glycosaminoglycan and heparan sulfate is not involved, MPS VI engages a purely somatic, connective-tissue arm and produces dysostosis multiplex, short stature, coarse facies, corneal clouding, cardiac valve disease, hepatosplenomegaly, airway obstruction, joint contractures, and carpal tunnel syndrome, while sparing primary central neurodegeneration and preserving intelligence. This preserved cognition distinguishes MPS VI from the heparan-sulfate-storing neuronopathic mucopolysaccharidoses. Enzyme replacement therapy with galsulfase (recombinant human ARSB, Naglazyme) is disease-modifying; hematopoietic stem cell transplantation and intensive multidisciplinary supportive care are also used.

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1
Mappings
1
Inheritance
4
Pathophys.
11
Phenotypes
17
Pathograph
1
Genes
3
Medical Actions
🔗

Mappings

MONDO
MONDO:0009661 mucopolysaccharidosis type 6
skos:exactMatch MONDO
👪

Inheritance

1
Autosomal recessive inheritance HP:0000007
MPS VI is an autosomal recessive lysosomal storage disorder; affected individuals carry biallelic pathogenic variants in ARSB.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:27814620 SUPPORT Human Clinical
"Mucopolysaccharidosis VI (MPS VI), or Maroteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme arylsulfatase B (ASB)."
This review directly supports autosomal recessive inheritance and ARSB deficiency as the cause of MPS VI.
PMID:18406185 SUPPORT In Vitro
"Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
This functional mutation study independently confirms autosomal recessive inheritance and ARSB as the deficient enzyme.
⚙

Pathophysiology

4
ARSB deficiency
Pathogenic variants in ARSB cause deficient N-acetylgalactosamine-4-sulfatase (arylsulfatase B) activity, blocking the lysosomal degradation of dermatan sulfate. This is the proximal enzymatic lesion of MPS VI.
ARSB hgnc:714
glycosaminoglycan catabolic process GO:0006027 ↓ DECREASED
N-acetylgalactosamine-4-sulfatase activity GO:0003943 ↓ DECREASED
Downstream
Lysosomal dermatan sulfate accumulation Loss of ARSB activity leaves dermatan sulfate undegraded, so it accumulates within lysosomes.
Show evidence (2 references)
PMID:18406185 SUPPORT In Vitro
"Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
This directly identifies ARSB deficiency as the proximal defect that blocks dermatan sulfate degradation.
PMID:34948256 SUPPORT Human Clinical
"The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB)."
This review confirms that ARSB pathogenic variants cause the N-acetylgalactosamine-4-sulfatase deficiency underlying MPS VI.
Lysosomal dermatan sulfate accumulation
Undegraded dermatan sulfate (with chondroitin-4-sulfate) accumulates within lysosomes. Dermatan sulfate is the only glycosaminoglycan stored in MPS VI; heparan sulfate is not involved, so the chemical identity of the stored GAG selects the somatic, connective-tissue arm of the module and not the heparan-sulfate-driven neuronopathic arm.
fibroblast CL:0000057
lysosome GO:0005764
Downstream
Dermatan sulfate connective-tissue and ECM storage Lysosomal dermatan sulfate storage extends into connective-tissue fibroblasts and the extracellular matrix.
Show evidence (2 references)
PMID:34948256 SUPPORT Human Clinical
"The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity."
This directly supports intralysosomal accumulation of undegraded dermatan sulfate as the storage event in MPS VI.
PMID:35216110 SUPPORT Other
"Mucopolysaccharidoses are rare paediatric lysosomal storage disorders, characterised by accumulation of glycosaminoglycans within lysosomes"
This cross-MPS review defines intralysosomal GAG accumulation as the characterizing storage event shared with the module hub. Evidence source is OTHER because this is a cross-MPS review.
Dermatan sulfate connective-tissue and ECM storage
Undegraded dermatan sulfate accumulates in connective-tissue fibroblasts and the extracellular matrix of bone, cartilage, heart valve, cornea, and viscera. This is the somatic, connective-tissue arm of the MPS module and, because heparan sulfate is not stored, it produces no primary central neurodegeneration.
fibroblast CL:0000057 chondrocyte CL:0000138
extracellular matrix organization GO:0030198 ↕ DYSREGULATED
Downstream
Multisystem somatic disease Progressive connective-tissue and ECM dermatan sulfate storage culminates in multisystem somatic disease.
Show evidence (2 references)
PMID:34948256 SUPPORT Human Clinical
"Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
This supports dermatan sulfate storage in intracellular and extracellular compartments producing connective-tissue and multi-organ disease.
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
This documents progressive tissue GAG storage as the driver of multisystem connective-tissue disease in MPS VI.
Multisystem somatic disease
Accumulated dermatan sulfate in connective tissue and ECM produces a progressive multisystem somatic phenotype: dysostosis multiplex and short stature, coarse facies, corneal clouding, cardiac valve disease, hepatosplenomegaly, joint stiffness/contractures, carpal tunnel syndrome, and upper-airway obstruction. Intelligence is characteristically preserved, reflecting the absence of the heparan-sulfate-driven neuronopathic arm.
Downstream
Dysostosis multiplex Dermatan sulfate connective-tissue storage produces the dysostosis multiplex skeletal pattern.
Short stature Skeletal and cartilage involvement impairs linear growth.
Coarse facial features Soft-tissue and craniofacial connective-tissue storage produces coarse facial features.
Corneal opacity Corneal connective-tissue storage produces corneal clouding.
Abnormal heart valve morphology Cardiac-valve connective-tissue storage produces valvular thickening and dysfunction.
Hepatosplenomegaly Visceral glycosaminoglycan storage contributes to liver and spleen enlargement.
Upper airway obstruction Upper-airway soft-tissue storage and recurrent airway disease narrow the airway.
Joint stiffness Osteoarticular connective-tissue storage produces progressive joint stiffness.
Constrictive median neuropathy Storage-related connective-tissue thickening contributes to carpal tunnel compression.
Hearing impairment Ear and airway involvement contribute to conductive and sensorineural hearing impairment.
Spinal cord compression Skeletal and connective-tissue disease in the cervical spine produces spinal cord compression.
Show evidence (2 references)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
This directly supports the multisystem somatic disease that is the terminal node of the connective-tissue arm.
PMID:35216110 SUPPORT Other
"progressive build-up of sugars may lead to musculoskeletal abnormalities and multi-organ failure, and in others, to cognitive decline"
This cross-MPS review documents progression of GAG storage to musculoskeletal and multi-organ disease, the terminal somatic node; MPS VI engages the musculoskeletal/multi-organ pole without the cognitive-decline arm. Evidence source is OTHER because this is a cross-MPS review.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Maroteaux-Lamy syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

11
Cardiovascular 2
Abnormal heart valve morphology Abnormal heart valve morphology HP:0001654
Show evidence (1 reference)
PMID:27134829 SUPPORT Human Clinical
"the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT"
This case series documents valvular stenosis and regurgitation in MPS VI patients, supporting cardiac valve disease as a core manifestation.
Hepatosplenomegaly Hepatosplenomegaly HP:0001433
Show evidence (1 reference)
PMID:27134829 SUPPORT Human Clinical
"Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients."
Organomegaly assessed by liver and spleen size supports hepatosplenomegaly as an MPS VI feature responsive to ERT.
Ear 1
Hearing impairment Hearing impairment HP:0000365
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
Hearing impairment is part of the multisystem somatic GAG-storage manifestations described for MPS VI.
Eye 1
Corneal opacity Corneal opacity HP:0007957
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
Corneal clouding is a recognized component of the multisystem GAG-storage manifestations of MPS VI.
Head and Neck 1
Coarse facial features Coarse facial features HP:0000280
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
Coarse facies is part of the multisystem somatic GAG-storage phenotype described for MPS VI.
Musculoskeletal 2
Dysostosis multiplex Dysostosis multiplex HP:0000943
Show evidence (1 reference)
PMID:34948256 SUPPORT Human Clinical
"Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
This supports osteoarticular (skeletal) disease as an early and prominent feature, the substrate for dysostosis multiplex.
Joint stiffness Joint stiffness HP:0001387
Show evidence (1 reference)
PMID:27134829 SUPPORT Human Clinical
"Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%)."
Improvement in range of motion and joint stiffness scores on ERT documents joint stiffness as a baseline MPS VI manifestation.
Respiratory 1
Upper airway obstruction Upper airway obstruction HP:0002781
Show evidence (1 reference)
PMID:27134829 SUPPORT Human Clinical
"Four patients showed improved pulmonary function."
Improvement in pulmonary function on ERT supports baseline airway/respiratory compromise as an MPS VI manifestation.
Growth 1
Short stature Short stature HP:0004322
Show evidence (1 reference)
PMID:34948256 SUPPORT Human Clinical
"Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
This supports prominent osteoarticular involvement, the basis for growth impairment and short stature in MPS VI.
Other 2
Constrictive median neuropathy Constrictive median neuropathy HP:0012185
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
Carpal tunnel syndrome is a recognized connective-tissue manifestation within the multisystem GAG-storage spectrum of MPS VI.
Spinal cord compression Spinal cord compression HP:0002176
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
Compressive spinal cord disease is a recognized skeletal/connective-tissue complication within the multisystem GAG-storage spectrum of MPS VI.
🧬

Genetic Associations

1
ARSB (Causative)
Gene: ARSB hgnc:714
Show evidence (2 references)
PMID:34948256 SUPPORT Human Clinical
"The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB)."
This directly identifies ARSB as the causative gene encoding the deficient enzyme in MPS VI.
PMID:18406185 SUPPORT In Vitro
"In summary, all the ARSB mutations studied had a significant effect on enzyme activity, protein processing and/or mRNA stability."
This functional study confirms that ARSB pathogenic variants impair enzyme activity, processing, and mRNA stability, supporting ARSB as the causative gene.
💊

Medical Actions

3
Galsulfase enzyme replacement therapy
Action: Pharmacotherapy NCIT:C15986
Agent: galsulfase NCIT:C74207
Weekly intravenous recombinant human N-acetylgalactosamine-4-sulfatase (galsulfase, Naglazyme) replaces the deficient ARSB enzyme, reduces urinary glycosaminoglycan excretion, and improves endurance, mobility, joint and pulmonary function, and organomegaly. Avascular tissues such as cartilage, cornea, and cardiac valves remain only partially responsive.
Mechanism Target:
RESTORES ARSB deficiency — Recombinant galsulfase replaces the deficient lysosomal N-acetylgalactosamine-4-sulfatase enzyme.
Show evidence (1 reference)
PMID:16647419 SUPPORT Human Clinical
"Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001)."
The reduction in urinary GAG demonstrates restoration of the proximal enzymatic degradation step on galsulfase.
INHIBITS Lysosomal dermatan sulfate accumulation — Galsulfase reduces the systemic dermatan sulfate storage burden, reflected by falling urinary GAG.
Show evidence (1 reference)
PMID:27134829 SUPPORT Human Clinical
"A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response."
The decline in urinary GAG supports reduction of the dermatan sulfate storage burden downstream of enzyme replacement.
Show evidence (3 references)
PMID:16647419 SUPPORT Human Clinical
"rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile."
This phase 3 randomized placebo-controlled trial establishes galsulfase (rhASB) as efficacious enzyme replacement therapy for MPS VI.
PMID:16647419 SUPPORT Human Clinical
"After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo."
Quantitative endurance benefit in the pivotal trial supports galsulfase as disease-modifying for the functional burden of MPS VI.
PMID:27134829 SUPPORT Human Clinical
"Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI."
This long-term case series supports durable benefit and safety of galsulfase ERT in MPS VI.
Hematopoietic stem cell transplantation
Action: hematopoietic stem cell transplantation MAXO:0000747
Hematopoietic stem cell transplantation provides a source of enzyme-competent cells and has been used in MPS VI, particularly where enzyme replacement therapy is unavailable or for severe early-onset disease.
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"The management of MPS VI involves enzyme replacement therapy and medical and surgical treatment of disease manifestations."
This review situates transplantation and other interventions within the multimodal management of MPS VI alongside enzyme replacement therapy.
Supportive and multidisciplinary care
Action: supportive care MAXO:0000950
Medical and surgical management of disease manifestations (cardiac, airway, skeletal, ophthalmologic, and carpal tunnel) is required to manage the progressive multisystem burden of MPS VI.
Show evidence (1 reference)
PMID:27814620 SUPPORT Human Clinical
"The management of MPS VI involves enzyme replacement therapy and medical and surgical treatment of disease manifestations."
This directly supports medical and surgical supportive management of MPS VI disease manifestations.
🔬

Biochemical Markers

1
Dermatan sulfate (Elevated)
Context: Undegraded dermatan sulfate is the primary stored glycosaminoglycan in MPS VI and is elevated in urine and tissues, reflecting the ARSB enzymatic block.
Show evidence (2 references)
PMID:18406185 SUPPORT In Vitro
"Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
This directly identifies dermatan sulfate as the substrate that accumulates because of ARSB deficiency in MPS VI.
PMID:27134829 SUPPORT Human Clinical
"A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response."
Elevated urinary GAG (dermatan sulfate) at baseline, falling on ERT, supports dermatan sulfate as the storage biomarker of MPS VI.
{ }

Source YAML

click to show 
name: Maroteaux-Lamy syndrome
creation_date: "2026-06-12T00:00:00Z"
category: Mendelian
description: >-
  Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS VI), is an
  autosomal recessive lysosomal storage disorder caused by deficient activity of
  N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ARSB). ARSB deficiency
  blocks lysosomal degradation of dermatan sulfate, leading to intracellular and
  extracellular accumulation of undegraded dermatan sulfate (with
  chondroitin-4-sulfate) in connective-tissue fibroblasts and the extracellular
  matrix of bone, cartilage, heart valve, cornea, and viscera. Because dermatan
  sulfate is the only stored glycosaminoglycan and heparan sulfate is not
  involved, MPS VI engages a purely somatic, connective-tissue arm and produces
  dysostosis multiplex, short stature, coarse facies, corneal clouding, cardiac
  valve disease, hepatosplenomegaly, airway obstruction, joint contractures, and
  carpal tunnel syndrome, while sparing primary central neurodegeneration and
  preserving intelligence. This preserved cognition distinguishes MPS VI from the
  heparan-sulfate-storing neuronopathic mucopolysaccharidoses. Enzyme replacement
  therapy with galsulfase (recombinant human ARSB, Naglazyme) is
  disease-modifying; hematopoietic stem cell transplantation and intensive
  multidisciplinary supportive care are also used.
disease_term:
  preferred_term: Maroteaux-Lamy syndrome
  term:
    id: MONDO:0009661
    label: mucopolysaccharidosis type 6
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0009661
      label: mucopolysaccharidosis type 6
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
parents:
- Mucopolysaccharidosis
- Lysosomal Storage Disorder
synonyms:
- Maroteaux-Lamy disease
- mucopolysaccharidosis type VI
- MPS VI
- arylsulfatase B deficiency
- N-acetylgalactosamine-4-sulfatase deficiency
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    MPS VI is an autosomal recessive lysosomal storage disorder; affected
    individuals carry biallelic pathogenic variants in ARSB.
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mucopolysaccharidosis VI (MPS VI), or Maroteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme arylsulfatase B (ASB)."
    explanation: This review directly supports autosomal recessive inheritance and ARSB deficiency as the cause of MPS VI.
  - reference: PMID:18406185
    reference_title: "Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
    explanation: This functional mutation study independently confirms autosomal recessive inheritance and ARSB as the deficient enzyme.
pathophysiology:
- name: ARSB deficiency
  description: >-
    Pathogenic variants in ARSB cause deficient N-acetylgalactosamine-4-sulfatase
    (arylsulfatase B) activity, blocking the lysosomal degradation of dermatan
    sulfate. This is the proximal enzymatic lesion of MPS VI.
  genes:
  - preferred_term: ARSB
    term:
      id: hgnc:714
      label: ARSB
  molecular_functions:
  - preferred_term: N-acetylgalactosamine-4-sulfatase activity
    modifier: DECREASED
    term:
      id: GO:0003943
      label: N-acetylgalactosamine-4-sulfatase activity
  biological_processes:
  - preferred_term: glycosaminoglycan catabolic process
    modifier: DECREASED
    term:
      id: GO:0006027
      label: glycosaminoglycan catabolic process
  evidence:
  - reference: PMID:18406185
    reference_title: "Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
    explanation: This directly identifies ARSB deficiency as the proximal defect that blocks dermatan sulfate degradation.
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB)."
    explanation: This review confirms that ARSB pathogenic variants cause the N-acetylgalactosamine-4-sulfatase deficiency underlying MPS VI.
  downstream:
  - target: Lysosomal dermatan sulfate accumulation
    causal_link_type: DIRECT
    description: Loss of ARSB activity leaves dermatan sulfate undegraded, so it accumulates within lysosomes.
    evidence:
    - reference: PMID:34948256
      reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity."
      explanation: This directly links the ARSB enzyme deficit to accumulation of undegraded dermatan sulfate.
- name: Lysosomal dermatan sulfate accumulation
  conforms_to: "mps_gag_storage#Lysosomal GAG Accumulation"
  description: >-
    Undegraded dermatan sulfate (with chondroitin-4-sulfate) accumulates within
    lysosomes. Dermatan sulfate is the only glycosaminoglycan stored in MPS VI;
    heparan sulfate is not involved, so the chemical identity of the stored GAG
    selects the somatic, connective-tissue arm of the module and not the
    heparan-sulfate-driven neuronopathic arm.
  chemical_entities:
  - preferred_term: dermatan sulfate
    term:
      id: CHEBI:18376
      label: dermatan sulfate
    modifier: INCREASED
  cellular_components:
  - preferred_term: lysosome
    term:
      id: GO:0005764
      label: lysosome
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  evidence:
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity."
    explanation: This directly supports intralysosomal accumulation of undegraded dermatan sulfate as the storage event in MPS VI.
  - reference: PMID:35216110
    reference_title: "Innate Immunity in Mucopolysaccharide Diseases."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Mucopolysaccharidoses are rare paediatric lysosomal storage disorders, characterised by accumulation of glycosaminoglycans within lysosomes"
    explanation: This cross-MPS review defines intralysosomal GAG accumulation as the characterizing storage event shared with the module hub. Evidence source is OTHER because this is a cross-MPS review.
  downstream:
  - target: Dermatan sulfate connective-tissue and ECM storage
    causal_link_type: DIRECT
    description: Lysosomal dermatan sulfate storage extends into connective-tissue fibroblasts and the extracellular matrix.
    evidence:
    - reference: PMID:34948256
      reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
      explanation: This links intralysosomal and extracellular dermatan sulfate deposits to progressive connective-tissue and organ-system disease.
- name: Dermatan sulfate connective-tissue and ECM storage
  conforms_to: "mps_gag_storage#Dermatan Sulfate-Driven Connective-Tissue and ECM Storage"
  description: >-
    Undegraded dermatan sulfate accumulates in connective-tissue fibroblasts and
    the extracellular matrix of bone, cartilage, heart valve, cornea, and viscera.
    This is the somatic, connective-tissue arm of the MPS module and, because
    heparan sulfate is not stored, it produces no primary central
    neurodegeneration.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  - preferred_term: chondrocyte
    term:
      id: CL:0000138
      label: chondrocyte
  biological_processes:
  - preferred_term: extracellular matrix organization
    modifier: DYSREGULATED
    term:
      id: GO:0030198
      label: extracellular matrix organization
  evidence:
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
    explanation: This supports dermatan sulfate storage in intracellular and extracellular compartments producing connective-tissue and multi-organ disease.
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: This documents progressive tissue GAG storage as the driver of multisystem connective-tissue disease in MPS VI.
  downstream:
  - target: Multisystem somatic disease
    causal_link_type: DIRECT
    description: Progressive connective-tissue and ECM dermatan sulfate storage culminates in multisystem somatic disease.
    evidence:
    - reference: PMID:27814620
      reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
      explanation: This links progressive tissue storage to multisystem clinical disease, the terminal somatic node.
- name: Multisystem somatic disease
  conforms_to: "mps_gag_storage#Multisystem Somatic Disease"
  description: >-
    Accumulated dermatan sulfate in connective tissue and ECM produces a
    progressive multisystem somatic phenotype: dysostosis multiplex and short
    stature, coarse facies, corneal clouding, cardiac valve disease,
    hepatosplenomegaly, joint stiffness/contractures, carpal tunnel syndrome, and
    upper-airway obstruction. Intelligence is characteristically preserved,
    reflecting the absence of the heparan-sulfate-driven neuronopathic arm.
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: This directly supports the multisystem somatic disease that is the terminal node of the connective-tissue arm.
  - reference: PMID:35216110
    reference_title: "Innate Immunity in Mucopolysaccharide Diseases."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "progressive build-up of sugars may lead to musculoskeletal abnormalities and multi-organ failure, and in others, to cognitive decline"
    explanation: This cross-MPS review documents progression of GAG storage to musculoskeletal and multi-organ disease, the terminal somatic node; MPS VI engages the musculoskeletal/multi-organ pole without the cognitive-decline arm. Evidence source is OTHER because this is a cross-MPS review.
  downstream:
  - target: Dysostosis multiplex
    causal_link_type: DIRECT
    description: Dermatan sulfate connective-tissue storage produces the dysostosis multiplex skeletal pattern.
  - target: Short stature
    causal_link_type: DIRECT
    description: Skeletal and cartilage involvement impairs linear growth.
  - target: Coarse facial features
    causal_link_type: DIRECT
    description: Soft-tissue and craniofacial connective-tissue storage produces coarse facial features.
  - target: Corneal opacity
    causal_link_type: DIRECT
    description: Corneal connective-tissue storage produces corneal clouding.
  - target: Abnormal heart valve morphology
    causal_link_type: DIRECT
    description: Cardiac-valve connective-tissue storage produces valvular thickening and dysfunction.
  - target: Hepatosplenomegaly
    causal_link_type: DIRECT
    description: Visceral glycosaminoglycan storage contributes to liver and spleen enlargement.
  - target: Upper airway obstruction
    causal_link_type: DIRECT
    description: Upper-airway soft-tissue storage and recurrent airway disease narrow the airway.
  - target: Joint stiffness
    causal_link_type: DIRECT
    description: Osteoarticular connective-tissue storage produces progressive joint stiffness.
  - target: Constrictive median neuropathy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Storage-related connective-tissue thickening contributes to carpal tunnel compression.
    intermediate_mechanisms:
    - carpal tunnel narrowing
  - target: Hearing impairment
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Ear and airway involvement contribute to conductive and sensorineural hearing impairment.
    intermediate_mechanisms:
    - recurrent ear infections
    - glycosaminoglycan deposition in auditory structures
  - target: Spinal cord compression
    causal_link_type: DIRECT
    description: Skeletal and connective-tissue disease in the cervical spine produces spinal cord compression.
phenotypes:
- name: Dysostosis multiplex
  category: Skeletal
  description: >-
    MPS VI produces a progressive dysostosis multiplex pattern of skeletal
    dysplasia from dermatan sulfate storage in bone and cartilage.
  phenotype_term:
    preferred_term: Dysostosis multiplex
    term:
      id: HP:0000943
      label: Dysostosis multiplex
  evidence:
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
    explanation: This supports osteoarticular (skeletal) disease as an early and prominent feature, the substrate for dysostosis multiplex.
- name: Short stature
  category: Growth
  description: >-
    Impaired skeletal growth from dermatan sulfate storage in bone and cartilage
    produces short stature.
  phenotype_term:
    preferred_term: Short stature
    term:
      id: HP:0004322
      label: Short stature
  evidence:
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus."
    explanation: This supports prominent osteoarticular involvement, the basis for growth impairment and short stature in MPS VI.
- name: Coarse facial features
  category: Craniofacial
  description: >-
    Soft-tissue and skeletal dermatan sulfate storage produces the coarse facial
    features characteristic of MPS VI.
  phenotype_term:
    preferred_term: Coarse facial features
    term:
      id: HP:0000280
      label: Coarse facial features
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: Coarse facies is part of the multisystem somatic GAG-storage phenotype described for MPS VI.
- name: Corneal opacity
  category: Ophthalmic
  description: >-
    Corneal clouding from dermatan sulfate storage in corneal connective tissue
    is a characteristic feature of MPS VI.
  phenotype_term:
    preferred_term: Corneal opacity
    term:
      id: HP:0007957
      label: Corneal opacity
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: Corneal clouding is a recognized component of the multisystem GAG-storage manifestations of MPS VI.
- name: Abnormal heart valve morphology
  category: Cardiac
  description: >-
    Dermatan sulfate storage in cardiac valve connective tissue produces
    progressive valvular thickening and dysfunction.
  phenotype_term:
    preferred_term: Abnormal heart valve morphology
    term:
      id: HP:0001654
      label: Abnormal heart valve morphology
  evidence:
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT"
    explanation: This case series documents valvular stenosis and regurgitation in MPS VI patients, supporting cardiac valve disease as a core manifestation.
- name: Hepatosplenomegaly
  category: Gastrointestinal
  description: >-
    Visceral dermatan sulfate storage produces hepatosplenomegaly, which is
    responsive to enzyme replacement therapy.
  phenotype_term:
    preferred_term: Hepatosplenomegaly
    term:
      id: HP:0001433
      label: Hepatosplenomegaly
  evidence:
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients."
    explanation: Organomegaly assessed by liver and spleen size supports hepatosplenomegaly as an MPS VI feature responsive to ERT.
- name: Joint stiffness
  category: Musculoskeletal
  description: >-
    Connective-tissue dermatan sulfate storage produces joint stiffness and
    contractures with reduced range of motion.
  phenotype_term:
    preferred_term: Joint stiffness
    term:
      id: HP:0001387
      label: Joint stiffness
  evidence:
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%)."
    explanation: Improvement in range of motion and joint stiffness scores on ERT documents joint stiffness as a baseline MPS VI manifestation.
- name: Constrictive median neuropathy
  category: Neurologic
  description: >-
    Dermatan sulfate deposition in the carpal tunnel compresses the median nerve,
    producing carpal tunnel syndrome. This is a mechanical, secondary peripheral
    neuropathy, not a primary central neurodegeneration.
  phenotype_term:
    preferred_term: Carpal tunnel syndrome
    term:
      id: HP:0012185
      label: Constrictive median neuropathy
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: Carpal tunnel syndrome is a recognized connective-tissue manifestation within the multisystem GAG-storage spectrum of MPS VI.
- name: Upper airway obstruction
  category: Respiratory
  description: >-
    Dermatan sulfate storage in upper-airway and tracheal soft tissue together
    with craniofacial skeletal change produces airway obstruction and contributes
    to recurrent respiratory disease.
  phenotype_term:
    preferred_term: Upper airway obstruction
    term:
      id: HP:0002781
      label: Upper airway obstruction
  evidence:
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Four patients showed improved pulmonary function."
    explanation: Improvement in pulmonary function on ERT supports baseline airway/respiratory compromise as an MPS VI manifestation.
- name: Hearing impairment
  category: Otolaryngologic
  description: >-
    Hearing loss is a recurrent extra-skeletal manifestation that travels with
    the connective-tissue disease burden of MPS VI.
  phenotype_term:
    preferred_term: Hearing impairment
    term:
      id: HP:0000365
      label: Hearing impairment
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: Hearing impairment is part of the multisystem somatic GAG-storage manifestations described for MPS VI.
- name: Spinal cord compression
  category: Neurologic
  description: >-
    Dermatan sulfate storage in the cervical dura and ligaments, together with
    skeletal change, can narrow the spinal canal and compress the spinal cord;
    this is a mechanical compressive complication rather than primary
    neurodegeneration.
  phenotype_term:
    preferred_term: Spinal cord compression
    term:
      id: HP:0002176
      label: Spinal cord compression
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations."
    explanation: Compressive spinal cord disease is a recognized skeletal/connective-tissue complication within the multisystem GAG-storage spectrum of MPS VI.
biochemical:
- name: Dermatan sulfate
  presence: Elevated
  context: >-
    Undegraded dermatan sulfate is the primary stored glycosaminoglycan in MPS VI
    and is elevated in urine and tissues, reflecting the ARSB enzymatic block.
  evidence:
  - reference: PMID:18406185
    reference_title: "Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal disorder caused by deficiency of N-acetylgalactosamine-4-sulfatase (ARSB), which is required for the degradation of dermatan sulfate."
    explanation: This directly identifies dermatan sulfate as the substrate that accumulates because of ARSB deficiency in MPS VI.
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response."
    explanation: Elevated urinary GAG (dermatan sulfate) at baseline, falling on ERT, supports dermatan sulfate as the storage biomarker of MPS VI.
genetic:
- name: ARSB
  gene_term:
    preferred_term: ARSB
    term:
      id: hgnc:714
      label: ARSB
  association: Causative
  notes: >-
    ARSB encodes N-acetylgalactosamine-4-sulfatase (arylsulfatase B); biallelic
    loss-of-function variants cause MPS VI. More than 150 disease-causing variants
    have been reported, producing a wide phenotypic spectrum from slowly to
    rapidly progressing disease.
  evidence:
  - reference: PMID:34948256
    reference_title: "Mucopolysaccharidosis Type VI, an Updated Overview of the Disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB)."
    explanation: This directly identifies ARSB as the causative gene encoding the deficient enzyme in MPS VI.
  - reference: PMID:18406185
    reference_title: "Maroteaux-Lamy syndrome: functional characterization of pathogenic mutations and polymorphisms in the arylsulfatase B gene."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "In summary, all the ARSB mutations studied had a significant effect on enzyme activity, protein processing and/or mRNA stability."
    explanation: This functional study confirms that ARSB pathogenic variants impair enzyme activity, processing, and mRNA stability, supporting ARSB as the causative gene.
treatments:
- name: Galsulfase enzyme replacement therapy
  description: >-
    Weekly intravenous recombinant human N-acetylgalactosamine-4-sulfatase
    (galsulfase, Naglazyme) replaces the deficient ARSB enzyme, reduces urinary
    glycosaminoglycan excretion, and improves endurance, mobility, joint and
    pulmonary function, and organomegaly. Avascular tissues such as cartilage,
    cornea, and cardiac valves remain only partially responsive.
  therapeutic_modality: PROTEIN_REPLACEMENT
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: galsulfase
      term:
        id: NCIT:C74207
        label: Galsulfase
  evidence:
  - reference: PMID:16647419
    reference_title: "Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile."
    explanation: This phase 3 randomized placebo-controlled trial establishes galsulfase (rhASB) as efficacious enzyme replacement therapy for MPS VI.
  - reference: PMID:16647419
    reference_title: "Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo."
    explanation: Quantitative endurance benefit in the pivotal trial supports galsulfase as disease-modifying for the functional burden of MPS VI.
  - reference: PMID:27134829
    reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI."
    explanation: This long-term case series supports durable benefit and safety of galsulfase ERT in MPS VI.
  target_mechanisms:
  - target: ARSB deficiency
    treatment_effect: RESTORES
    description: Recombinant galsulfase replaces the deficient lysosomal N-acetylgalactosamine-4-sulfatase enzyme.
    evidence:
    - reference: PMID:16647419
      reference_title: "Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001)."
      explanation: The reduction in urinary GAG demonstrates restoration of the proximal enzymatic degradation step on galsulfase.
  - target: Lysosomal dermatan sulfate accumulation
    treatment_effect: INHIBITS
    description: Galsulfase reduces the systemic dermatan sulfate storage burden, reflected by falling urinary GAG.
    evidence:
    - reference: PMID:27134829
      reference_title: "Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response."
      explanation: The decline in urinary GAG supports reduction of the dermatan sulfate storage burden downstream of enzyme replacement.
- name: Hematopoietic stem cell transplantation
  description: >-
    Hematopoietic stem cell transplantation provides a source of enzyme-competent
    cells and has been used in MPS VI, particularly where enzyme replacement
    therapy is unavailable or for severe early-onset disease.
  treatment_term:
    preferred_term: hematopoietic stem cell transplantation
    term:
      id: MAXO:0000747
      label: hematopoietic stem cell transplantation
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The management of MPS VI involves enzyme replacement therapy and medical and surgical treatment of disease manifestations."
    explanation: This review situates transplantation and other interventions within the multimodal management of MPS VI alongside enzyme replacement therapy.
- name: Supportive and multidisciplinary care
  description: >-
    Medical and surgical management of disease manifestations (cardiac, airway,
    skeletal, ophthalmologic, and carpal tunnel) is required to manage the
    progressive multisystem burden of MPS VI.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:27814620
    reference_title: "Mucopolysaccharidosis VI: pathophysiology, diagnosis and treatment."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The management of MPS VI involves enzyme replacement therapy and medical and surgical treatment of disease manifestations."
    explanation: This directly supports medical and surgical supportive management of MPS VI disease manifestations.