Mucopolysaccharidosis type 7

Summary

Mucopolysaccharidosis type 7 (MONDO:0009662) is a disease caused by GUSB (GenCC Definitive), with 2 cohort genes and 13 clinical trials. Top therapeutic interventions include vestronidase alfa, cyclophosphamide anhydrous, and laronidase.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: GUSB (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 668
• Phenotypes (HPO): 26
• Clinical trials: 13

Clinical features

Epidemiology

Prevalence records

10 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.01	Europe	Validated
Point prevalence	<1 / 1 000 000	0.007	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.24	Netherlands	Validated
Prevalence at birth	<1 / 1 000 000	0.02	Brazil	Validated
Prevalence at birth	<1 / 1 000 000	0.02	Czech Republic	Validated
Prevalence at birth	<1 / 1 000 000	0.02	Japan	Validated
Prevalence at birth	<1 / 1 000 000	0.038	Switzerland	Validated
Prevalence at birth	<1 / 1 000 000	0.047	Australia	Validated
Prevalence at birth	<1 / 1 000 000	0.027	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.29	Canada	Validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0000023	Inguinal hernia	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0001004	Lymphedema	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001537	Umbilical hernia	Very frequent (80-99%)
HP:0001541	Ascites	Very frequent (80-99%)
HP:0002103	Abnormality of the pleura	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002650	Scoliosis	Very frequent (80-99%)
HP:0004607	Anterior beaking of lower thoracic vertebrae	Very frequent (80-99%)
HP:0005019	Diaphyseal thickening	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0008430	Anterior beaking of lumbar vertebrae	Very frequent (80-99%)
HP:0012368	Flat face	Very frequent (80-99%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001387	Joint stiffness	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0001840	Metatarsus adductus	Frequent (30-79%)
HP:0003272	Abnormality of the hip bone	Frequent (30-79%)
HP:0008155	Mucopolysacchariduria	Frequent (30-79%)
HP:0010655	Epiphyseal stippling	Frequent (30-79%)
HP:0012115	Hepatitis	Frequent (30-79%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0100026	Arteriovenous malformation	Occasional (5-29%)
HP:0100625	Enlarged thorax	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mucopolysaccharidosis type 7
Mondo ID	MONDO:0009662
MeSH	D016538
OMIM	253220
Orphanet	584
DOID	DOID:12803
ICD-11	1563668250
NCIT	C84903
SNOMED CT	43916004
UMLS	C0085132
MedGen	43108
GARD	0007096
MedDRA	10056893
NORD	1722
Is cancer (heuristic)	no

Also known as: Beta-glucuronidase deficiency · beta-glucuronidase deficiency · MPS VII · MPS7 · MPSVII · mucopolysaccharidosis type 7 · Mucopolysaccharidosis Type VII · mucopolysaccharidosis type VII · mucopolysaccharidosis, mps-VII · mucopolysaccharidosis, type VII · Sly disease · Sly syndrome

Data availability: 668 ClinVar variants · 5 GenCC gene-disease records · 7 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › lysosomal storage disease › mucopolysaccharidosis › mucopolysaccharidosis type 7

Related subtypes (7): mucopolysaccharidosis type 1, mucopolysaccharidosis type 6, mucopolysaccharidosis type 2, mucopolysaccharidosis type 9, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, mucopolysaccharidosis, type 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

345 likely benign, 129 uncertain significance, 42 pathogenic, 38 likely pathogenic, 17 conflicting classifications of pathogenicity, 11 benign, 10 pathogenic/likely pathogenic, 7 benign/likely benign, 1 conflicting classifications of pathogenicity; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
100722	NM_000181.4(GUSB):c.530C>T (p.Thr177Ile)	GUSB	Pathogenic	no assertion criteria provided
1027384	NM_000181.4(GUSB):c.1651C>T (p.Gln551Ter)	GUSB	Pathogenic	criteria provided, single submitter
1074941	NM_000181.4(GUSB):c.163C>T (p.Arg55Ter)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339516	NM_000181.4(GUSB):c.1832G>A (p.Arg611Gln)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339727	NM_000181.4(GUSB):c.1145G>A (p.Arg382His)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2045917	NM_000181.4(GUSB):c.738C>G (p.Tyr246Ter)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2087077	NM_000181.4(GUSB):c.932dup (p.Ser312fs)	GUSB	Pathogenic	criteria provided, single submitter
2111403	NM_000181.4(GUSB):c.24del (p.Trp9fs)	GUSB	Pathogenic	criteria provided, single submitter
2117122	NM_000181.4(GUSB):c.604C>T (p.Gln202Ter)	GUSB	Pathogenic	criteria provided, single submitter
2431204	NM_000181.4(GUSB):c.1874del (p.Arg625fs)	GUSB	Pathogenic	criteria provided, single submitter
2431211	NM_000181.4(GUSB):c.7del (p.Arg3fs)	GUSB	Pathogenic	criteria provided, single submitter
2501051	NM_000181.4(GUSB):c.724+1G>T	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2636656	NM_000181.4(GUSB):c.581+1G>A	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2698405	NM_000181.4(GUSB):c.867_871del (p.Trp289_Tyr291delinsTer)	GUSB	Pathogenic	criteria provided, single submitter
2701335	NM_000181.4(GUSB):c.643C>T (p.Gln215Ter)	GUSB	Pathogenic	criteria provided, single submitter
2728754	NM_000181.4(GUSB):c.74dup (p.Gly26fs)	GUSB	Pathogenic	criteria provided, single submitter
2731024	NM_000181.4(GUSB):c.1455dup (p.Asn486Ter)	GUSB	Pathogenic	criteria provided, multiple submitters, no conflicts
2735027	NM_000181.4(GUSB):c.1457_1460del (p.Asn486fs)	GUSB	Pathogenic	criteria provided, single submitter
2736760	NM_000181.4(GUSB):c.1047del (p.Asn349fs)	GUSB	Pathogenic	criteria provided, single submitter
2743822	NM_000181.4(GUSB):c.91C>T (p.Gln31Ter)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2755268	NM_000181.4(GUSB):c.190del (p.Tyr64fs)	GUSB	Pathogenic	criteria provided, single submitter
2757736	NM_000181.4(GUSB):c.1809dup (p.Asn604fs)	GUSB	Pathogenic	criteria provided, single submitter
2766408	NM_000181.4(GUSB):c.1872_1875dup (p.Tyr626fs)	GUSB	Pathogenic	criteria provided, single submitter
2797791	NM_000181.4(GUSB):c.320del (p.Leu107fs)	GUSB	Pathogenic	criteria provided, single submitter
2799488	NM_000181.4(GUSB):c.916C>T (p.Gln306Ter)	GUSB	Pathogenic	criteria provided, single submitter
2803581	NM_000181.4(GUSB):c.739C>T (p.Gln247Ter)	GUSB	Pathogenic	criteria provided, single submitter
2806625	NM_000181.4(GUSB):c.11_12del (p.Gly4fs)	GUSB	Pathogenic	criteria provided, single submitter
2841797	NM_000181.4(GUSB):c.76_79dup (p.Met27fs)	GUSB	Pathogenic	criteria provided, single submitter
2847045	NM_000181.4(GUSB):c.1865T>A (p.Leu622Ter)	GUSB	Pathogenic	criteria provided, single submitter
2848108	NC_000007.14:g.65974442del	GUSB	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GUSB	Definitive	Autosomal recessive	mucopolysaccharidosis type 7	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUSB	Orphanet:584	Mucopolysaccharidosis type 7
ASL	Orphanet:23	Argininosuccinic aciduria

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GUSB	HGNC:4696	ENSG00000169919	P08236	Beta-glucuronidase	gencc,clinvar
ASL	HGNC:746	ENSG00000126522	P04424	Argininosuccinate lyase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUSB	Beta-glucuronidase	Plays an important role in the degradation of dermatan and keratan sulfates.
ASL	Argininosuccinate lyase	Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine sy…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	14.6×	0.135
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GUSB	Antibody/Immunoglobulin	yes	3.2.1.31	Glyco_hydro_2, Ig-like_GH2, Glyco_hydro_2_cat
ASL	Enzyme (other)	yes	4.3.2.1	Fumarate_lyase_fam, L-Aspartase-like, Argininosuccinate_lyase

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endometrium epithelium	1
tendon of biceps brachii	1
tibia	1
liver	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUSB	297	ubiquitous	marker	endometrium epithelium, tendon of biceps brachii, tibia
ASL	145	ubiquitous	marker	right lobe of liver, liver, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUSB	3,659
ASL	1,486

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GUSB	P08236	2
ASL	P04424	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS VII - Sly syndrome (Hyaluronan metabolism)	1	5710.0×	0.001	GUSB
MPS VII - Sly syndrome (CS/DS degradation)	1	5710.0×	0.001	GUSB
ASL variants cause argininosuccinate aciduria	1	5710.0×	0.001	ASL
Mucopolysaccharidoses	1	951.7×	0.005	GUSB
Hyaluronan metabolism	1	475.8×	0.007	GUSB
Urea cycle	1	439.2×	0.007	ASL
Diseases of carbohydrate metabolism	1	407.9×	0.007	GUSB
Hyaluronan degradation	1	356.9×	0.007	GUSB
Heparan sulfate/heparin (HS-GAG) metabolism	1	271.9×	0.007	GUSB
CS/DS degradation	1	271.9×	0.007	GUSB
HS-GAG degradation	1	248.3×	0.007	GUSB
Metabolism	2	11.6×	0.012	GUSB, ASL
Glycosaminoglycan metabolism	1	109.8×	0.014	GUSB
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.024	GUSB
Diseases of metabolism	1	40.2×	0.033	GUSB
Metabolism of amino acids and derivatives	1	33.8×	0.037	ASL
Innate Immune System	1	12.8×	0.090	GUSB
Neutrophil degranulation	1	11.5×	0.094	GUSB
Disease	1	6.5×	0.148	GUSB
Immune System	1	6.5×	0.148	GUSB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
ammonia assimilation cycle	1	8426.0×	0.003	ASL
growth plate cartilage morphogenesis	1	4213.0×	0.003	GUSB
obsolete L-arginine biosynthetic process via ornithine	1	4213.0×	0.003	ASL
L-arginine biosynthetic process	1	2808.7×	0.003	ASL
muscle system process	1	2106.5×	0.003	GUSB
chondrocyte hypertrophy	1	1685.2×	0.003	GUSB
chondroitin sulfate proteoglycan catabolic process	1	1404.3×	0.003	GUSB
glycosaminoglycan catabolic process	1	1203.7×	0.003	GUSB
arginine metabolic process	1	1203.7×	0.003	ASL
articular cartilage development	1	1203.7×	0.003	GUSB
heparan sulfate proteoglycan catabolic process	1	936.2×	0.003	GUSB
urea cycle	1	648.1×	0.004	ASL
phosphatidylinositol-3-phosphate biosynthetic process	1	648.1×	0.004	GUSB
hyaluronan catabolic process	1	495.6×	0.005	GUSB
cranial skeletal system development	1	468.1×	0.005	GUSB
TORC1 signaling	1	401.2×	0.006	GUSB
homeostasis of number of cells	1	337.0×	0.006	GUSB
bone resorption	1	290.6×	0.007	GUSB
aorta development	1	280.9×	0.007	GUSB
endochondral ossification	1	271.8×	0.007	GUSB
retinoid metabolic process	1	247.8×	0.007	GUSB
positive regulation of nitric oxide biosynthetic process	1	227.7×	0.007	ASL
response to peptide hormone	1	195.9×	0.008	GUSB
protein localization to nucleus	1	175.5×	0.009	GUSB
lysosome organization	1	153.2×	0.009	GUSB
energy homeostasis	1	135.9×	0.010	GUSB
protein secretion	1	131.7×	0.010	GUSB
post-embryonic development	1	102.8×	0.012	ASL
locomotory behavior	1	89.6×	0.014	ASL
multicellular organism growth	1	68.5×	0.017	GUSB

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Vestronidase Alfa	Approved (phase 4)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GUSB	PRASTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GUSB	2	4
ASL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PRASTERONE	4	GUSB
KAEMPFEROL	1	GUSB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GUSB	41	Binding:38, ADMET:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GUSB	3.2.1.31	beta-glucuronidase
ASL	4.3.2.1	argininosuccinate lyase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PRASTERONE	4	GUSB
KAEMPFEROL	1	GUSB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GUSB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ASL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ASL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2	4
PHASE3	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02230566	PHASE3	COMPLETED	A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
NCT02432144	PHASE3	COMPLETED	A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT00668564	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism
NCT01043640	PHASE2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT01856218	PHASE1/PHASE2	COMPLETED	An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of Study Drug UX003 Recombinant Human Beta-glucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
NCT02418455	PHASE2	COMPLETED	Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Treatment in Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7) Patients Less Than 5 Years of Age
NCT04532047	PHASE1	RECRUITING	PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
NCT03604835	Not specified	RECRUITING	Mucopolysaccharidosis VII Disease Monitoring Program
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03775174	Not specified	AVAILABLE	Expanded Access to Mepsevii
NCT01870375	Not specified	COMPLETED	Longitudinal Studies of Brain Structure and Function in MPS Disorders
NCT02097251	Not specified	NO_LONGER_AVAILABLE	An Open-Label Treatment Protocol With UX003 rhGUS Enzyme Replacement Therapy for an Advanced Stage MPS 7 Patient

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VESTRONIDASE ALFA	4	6
CYCLOPHOSPHAMIDE ANHYDROUS	4	2
LARONIDASE	4	1