Scheie syndrome

Summary

Scheie syndrome (MONDO:0011760) is a disease caused by IDUA (GenCC Definitive), with 2 cohort genes and 8 clinical trials. Top therapeutic interventions include laronidase.

At a glance

• Prevalence: 1-9 / 1 000 000 (Canada) [Orphanet-validated]
• Causal gene: IDUA (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 106
• Phenotypes (HPO): 18
• Clinical trials: 8

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.2	Canada	Validated
Point prevalence	<1 / 1 000 000	0.07	United Kingdom	Validated
Prevalence at birth	1-9 / 1 000 000	0.2	Canada	Validated
Prevalence at birth	<1 / 1 000 000	0.07	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000501	Glaucoma	Very frequent (80-99%)
HP:0000924	Abnormality of the skeletal system	Very frequent (80-99%)
HP:0001376	Limitation of joint mobility	Very frequent (80-99%)
HP:0001659	Aortic regurgitation	Very frequent (80-99%)
HP:0007957	Corneal opacity	Very frequent (80-99%)
HP:0008155	Mucopolysacchariduria	Very frequent (80-99%)
HP:0040129	Abnormal nerve conduction velocity	Very frequent (80-99%)
HP:0100021	Cerebral palsy	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)
HP:0000280	Coarse facial features	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0012471	Thick vermilion border	Frequent (30-79%)
HP:0000154	Wide mouth	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0002313	Spastic paraparesis	Occasional (5-29%)
HP:0012384	Rhinitis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Scheie syndrome
Mondo ID	MONDO:0011760
OMIM	607016
Orphanet	93474
DOID	DOID:0060222
NCIT	C61265
SNOMED CT	73123008
UMLS	C0026708
MedGen	6453
GARD	0012561
Is cancer (heuristic)	no

Also known as: MPS I S · MPS1-S · MPS1S · MPS5, formerly · MPSIS · mucopolysaccharidosis Is · mucopolysaccharidosis type 1S · mucopolysaccharidosis type IS · Scheie syndrome

Data availability: 106 ClinVar variants · 4 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › mucopolysaccharidosis type 1 › Scheie syndrome

Related subtypes (2): Hurler syndrome, Hurler-Scheie syndrome

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

106 retrieved; paginated sample, class counts are floors:

28 pathogenic, 23 likely pathogenic, 18 uncertain significance, 14 benign, 13 pathogenic/likely pathogenic, 10 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
11908	NM_000203.5(IDUA):c.1205G>A (p.Trp402Ter)	IDUA	Pathogenic	reviewed by expert panel
11910	NM_000203.5(IDUA):c.1598C>G (p.Pro533Arg)	IDUA	Pathogenic	reviewed by expert panel
11917	NM_000203.5(IDUA):c.1861C>T (p.Arg621Ter)	IDUA	Pathogenic	reviewed by expert panel
11922	NM_000203.5(IDUA):c.266G>A (p.Arg89Gln)	IDUA	Pathogenic	reviewed by expert panel
11925	NM_000203.5(IDUA):c.1091C>T (p.Thr364Met)	IDUA	Pathogenic	reviewed by expert panel
11927	NM_000203.5(IDUA):c.1037T>G (p.Leu346Arg)	IDUA	Pathogenic	criteria provided, multiple submitters, no conflicts
1323100	NM_000203.5(IDUA):c.603C>G (p.Tyr201Ter)	IDUA	Pathogenic	reviewed by expert panel
1454082	NM_000203.5(IDUA):c.1815dup (p.Val606fs)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167190	NM_000203.5(IDUA):c.979G>C (p.Ala327Pro)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167191	NM_000203.5(IDUA):c.1614del (p.His539fs)	IDUA	Pathogenic	reviewed by expert panel
193061	NM_000203.5(IDUA):c.152G>A (p.Gly51Asp)	IDUA	Pathogenic	reviewed by expert panel
2203495	NM_000203.5(IDUA):c.532G>A (p.Glu178Lys)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
222994	NM_000203.5(IDUA):c.386-2A>G	IDUA	Pathogenic	reviewed by expert panel
222995	NM_000203.5(IDUA):c.653T>C (p.Leu218Pro)	IDUA	Pathogenic	reviewed by expert panel
222996	NM_000203.5(IDUA):c.590-7G>A	IDUA	Pathogenic	reviewed by expert panel
2506987	NM_000203.5(IDUA):c.34_46del (p.Ala12fs)	IDUA	Pathogenic	criteria provided, single submitter
2734639	NM_000203.5(IDUA):c.1190-1del	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280976	NM_000203.5(IDUA):c.1855C>T (p.Arg619Ter)	IDUA	Pathogenic	reviewed by expert panel
3391404	NM_000203.5(IDUA):c.1853_1855del (p.Tyr618_Arg619delinsTer)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3591559	NM_000203.5(IDUA):c.1264del (p.Ala422fs)	IDUA	Pathogenic	criteria provided, single submitter
3591564	NM_000203.5(IDUA):c.1743C>A (p.Tyr581Ter)	IDUA	Pathogenic	criteria provided, single submitter
550382	NM_000203.5(IDUA):c.878_889dup (p.Thr293_Tyr296dup)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550799	NM_000203.5(IDUA):c.1139A>G (p.Gln380Arg)	IDUA	Pathogenic	reviewed by expert panel
552333	NM_000203.5(IDUA):c.606C>A (p.Tyr202Ter)	IDUA	Pathogenic	reviewed by expert panel
552506	NM_000203.5(IDUA):c.1602del (p.Leu535fs)	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
556406	NM_000203.5(IDUA):c.1898C>T (p.Ser633Leu)	IDUA	Pathogenic	criteria provided, multiple submitters, no conflicts
556504	NM_000203.5(IDUA):c.1190-2A>T	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
556527	NM_000203.5(IDUA):c.1828+1G>C	IDUA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
557885	NM_000203.5(IDUA):c.1045_1047del (p.Asp349del)	IDUA	Pathogenic	reviewed by expert panel
558189	NM_000203.5(IDUA):c.1148G>A (p.Arg383His)	IDUA	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 3 · 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
IDUA	Definitive	Autosomal recessive	Scheie syndrome	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IDUA	Orphanet:93473	Hurler syndrome
IDUA	Orphanet:93474	Scheie syndrome
IDUA	Orphanet:93476	Hurler-Scheie syndrome

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
IDUA	HGNC:5391	ENSG00000127415	P35475	Alpha-L-iduronidase	gencc,clinvar
SLC26A1	HGNC:10993	ENSG00000145217	Q9H2B4	Sulfate anion transporter 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC26A1	Sulfate anion transporter 1	Sodium-independent sulfate anion transporter.

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
Transporter	1	38.9×	0.051
Antibody/Immunoglobulin	1	14.6×	0.067

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IDUA	Antibody/Immunoglobulin	yes	3.2.1.76	Glyco_hydro_39, Ig-like_fold, GH_hydrolase_sf
SLC26A1	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
left adrenal gland cortex	1
right adrenal gland cortex	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IDUA	209	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SLC26A1	156	tissue_specific	yes	right adrenal gland cortex, left adrenal gland cortex, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IDUA	1,927
SLC26A1	1,454

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IDUA	P35475	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC26A1	Q9H2B4	83.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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 I - Hurler syndrome (HS-GAG degradation)	1	5710.0×	0.001	IDUA
MPS I - Hurler syndrome (CS/DS degradation)	1	5710.0×	0.001	IDUA
Transport and metabolism of PAPS	1	815.7×	0.006	SLC26A1
Inorganic anion exchange by SLC26 transporters	1	634.4×	0.006	SLC26A1
CS/DS degradation	1	271.9×	0.009	IDUA
Cytosolic sulfonation of small molecules	1	259.6×	0.009	SLC26A1
HS-GAG degradation	1	248.3×	0.009	IDUA
Phase II - Conjugation of compounds	1	139.3×	0.013	SLC26A1
Glycosaminoglycan metabolism	1	109.8×	0.015	SLC26A1
Biological oxidations	1	64.9×	0.021	SLC26A1
R-HSA-425393	1	64.9×	0.021	SLC26A1
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.021	SLC26A1
SLC-mediated transmembrane transport	1	29.6×	0.039	SLC26A1
Transport of small molecules	1	12.6×	0.083	SLC26A1
Metabolism	1	5.8×	0.165	SLC26A1

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
disaccharide metabolic process	1	8426.0×	5e-04	IDUA
heparin proteoglycan catabolic process	1	8426.0×	5e-04	IDUA
dermatan sulfate proteoglycan catabolic process	1	2106.5×	0.001	IDUA
glycosaminoglycan catabolic process	1	1203.7×	0.001	IDUA
oxalate transport	1	1203.7×	0.001	SLC26A1
heparan sulfate proteoglycan catabolic process	1	936.2×	0.002	IDUA
sulfate transmembrane transport	1	601.9×	0.002	SLC26A1
chloride transport	1	227.7×	0.005	SLC26A1
chloride transmembrane transport	1	118.7×	0.008	SLC26A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IDUA	0	0
SLC26A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
IDUA	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
IDUA	3.2.1.76	L-iduronidase

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	IDUA
D	Druggable family + AlphaFold only, no drug	1	SLC26A1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IDUA	15	—
SLC26A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	2
PHASE1	2
PHASE4	1
PHASE2	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00144781	PHASE4	COMPLETED	A Dose-optimization Study of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I (MPS I) Disease
NCT00146770	PHASE3	COMPLETED	Phase 3 Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients
NCT00258011	PHASE3	COMPLETED	Study of Aldurazyme® Replacement Therapy in Patients With Mucopolysaccharidosis I (MPS I) Disease
NCT00146757	PHASE2	COMPLETED	A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old
NCT05665036	PHASE1/PHASE2	WITHDRAWN	Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy
NCT05682144	PHASE1	RECRUITING	ISP-001: Sleeping Beauty Transposon-Engineered B Cells for MPS I
NCT00786968	PHASE1	TERMINATED	Extension Study of Intrathecal Enzyme Replacement Therapy for MPS I
NCT00852358	Not specified	COMPLETED	A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LARONIDASE	4	3