Congenital sucrase-isomaltase deficiency

Summary

Congenital sucrase-isomaltase deficiency (MONDO:0009114) is a disease (an umbrella term covering 6 Mondo subtypes) caused by SI (GenCC Strong), with 1 cohort gene and 10 clinical trials.

At a glance

• Prevalence: 1-5 / 10 000 (Europe)
• Causal gene: SI (GenCC Strong)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 513
• Phenotypes (HPO): 14
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	20	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0002014	Diarrhea	Very frequent (80-99%)
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002018	Nausea	Frequent (30-79%)
HP:0002019	Constipation	Frequent (30-79%)
HP:0002020	Gastroesophageal reflux	Frequent (30-79%)
HP:0004396	Poor appetite	Frequent (30-79%)
HP:0033589	Flatulence	Frequent (30-79%)
HP:0002607	Bowel incontinence	Occasional (5-29%)
HP:0003270	Abdominal distention	Occasional (5-29%)
HP:0011848	Abdominal colic	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0025085	Bloody diarrhea	Occasional (5-29%)
HP:0001508	Failure to thrive	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital sucrase-isomaltase deficiency
Mondo ID	MONDO:0009114
MeSH	C538139
OMIM	222900
Orphanet	35122
DOID	DOID:0111633
ICD-11	1817406536
NCIT	C128190
SNOMED CT	78373000
UMLS	C1283620
MedGen	220924
GARD	0006183
MedDRA	10066387
NORD	1056
Is cancer (heuristic)	no

Also known as: congenital sucrase-isomaltase deficiency · congenital sucrose intolerance · congenital sucrose-isomaltase malabsorption · CSID · disaccharide intolerance · disaccharide intolerance, 1 · genetic sucrase-isomaltose malabsorption · sucrase-isomaltase deficiency · sucrase-isomaltase deficiency, congenital · sucrose intolerance congenital · sucrose isomaltose enzyme deficiency · sucrose-isomaltase malabsorption, congenital

Data availability: 513 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › malabsorption syndrome › intestinal disaccharidase deficiency › congenital sucrase-isomaltase deficiency

Subtypes (6): congenital sucrase-isomaltase deficiency with starch intolerance, congenital sucrase-isomaltase deficiency with minimal starch tolerance, congenital sucrase-isomaltase deficiency without starch intolerance, congenital sucrase-isomaltase deficiency with starch and lactose intolerance, congenital sucrase-isomaltase deficiency without sucrose intolerance, global disaccharide intolerance

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

513 retrieved; paginated sample, class counts are floors:

283 uncertain significance, 79 conflicting classifications of pathogenicity, 45 likely pathogenic, 36 likely benign, 25 benign/likely benign, 18 benign, 18 pathogenic/likely pathogenic, 9 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1179095	NM_001041.4(SI):c.2025dup (p.Gly676fs)	SI	Pathogenic	criteria provided, single submitter
1179179	NM_001041.4(SI):c.793del (p.Gln265fs)	SI	Pathogenic	criteria provided, single submitter
1323594	NM_001041.4(SI):c.2242C>T (p.Gln748Ter)	SI	Pathogenic	criteria provided, single submitter
1355490	NM_001041.4(SI):c.2865C>A (p.Cys955Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380031	NM_001041.4(SI):c.832C>T (p.Gln278Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1382544	NM_001041.4(SI):c.1837G>T (p.Glu613Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413	NM_001041.4(SI):c.1022T>C (p.Leu341Pro)	SI	Pathogenic	no assertion criteria provided
1414	NM_001041.4(SI):c.350A>G (p.Gln117Arg)	SI	Pathogenic	no assertion criteria provided
1415	NM_001041.4(SI):c.1859T>C (p.Leu620Pro)	SI	Pathogenic	no assertion criteria provided
1416	NM_001041.4(SI):c.3686G>A (p.Cys1229Tyr)	SI	Pathogenic	no assertion criteria provided
1420526	NM_001041.4(SI):c.3532C>T (p.Gln1178Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454102	NM_001041.4(SI):c.3229C>T (p.Arg1077Ter)	SI	Pathogenic	criteria provided, multiple submitters, no conflicts
1951236	NM_001041.4(SI):c.834_837del (p.Gln278fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1987170	NM_001041.4(SI):c.2028dup (p.Gln677fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2030530	NM_001041.4(SI):c.2945_2946del (p.Ser982fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2114756	NM_001041.4(SI):c.1023del (p.Val342fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2139072	NM_001041.4(SI):c.4208_4223del (p.Asn1403fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2193206	NM_001041.4(SI):c.1910delinsGTCTTC (p.Phe637fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203459	NM_001041.4(SI):c.273_274del (p.Gly92fs)	SI	Pathogenic	criteria provided, multiple submitters, no conflicts
2873574	NM_001041.4(SI):c.4094dup (p.Phe1366fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3588800	NM_001041.4(SI):c.3629dup (p.His1210fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
418676	NM_001041.4(SI):c.3186_3187del (p.Leu1062_Tyr1063insTer)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
432014	NM_001041.4(SI):c.3370C>T (p.Arg1124Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
489002	NM_001041.4(SI):c.853G>T (p.Glu285Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
591922	NM_001041.4(SI):c.2654_2657del (p.Asp885fs)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631912	NM_001041.4(SI):c.2401G>T (p.Glu801Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984937	NM_001041.4(SI):c.4825C>T (p.Arg1609Ter)	SI	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067337	NM_001041.4(SI):c.635+2T>C	SI	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179169	GRCh37/hg19 3q26.1(chr3:164714302-164716481)	SI	Likely pathogenic	no assertion criteria provided
1179208	GRCh37/hg19 3q26.1(chr3:164696665-164751252)	SI	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
SI	Strong	Autosomal recessive	congenital sucrase-isomaltase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SI	Orphanet:35122	Congenital sucrase-isomaltase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SI	HGNC:10856	ENSG00000090402	P14410	Sucrase-isomaltase, intestinal	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SI	Sucrase-isomaltase, intestinal	Plays an important role in the final stage of carbohydrate digestion.

Protein-family classification

Druggable: 1 · 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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SI	Enzyme (other)	yes	3.2.1.10	Glyco_hydro_31_TIM, P_trefoil_dom, Gal_mutarotase_sf_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
ileum	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SI	66	tissue_specific	marker	jejunal mucosa, ileal mucosa, ileum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SI	2,409

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SI	P14410	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Intestinal saccharidase deficiencies	1	5710.0×	0.001	SI
Digestion of dietary carbohydrate	1	951.7×	0.002	SI
Diseases of carbohydrate metabolism	1	815.7×	0.002	SI
Digestion and absorption	1	761.3×	0.002	SI
Digestion	1	571.0×	0.002	SI
Diseases of metabolism	1	80.4×	0.015	SI
Disease	1	13.1×	0.076	SI

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
sucrose catabolic process	1	16852.0×	1e-04	SI
polysaccharide digestion	1	4213.0×	2e-04	SI

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
SI	MIGLUSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SI	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MIGLUSTAT	4	SI
MIGALASTAT	4	SI
MIGLITOL	4	SI
ACARBOSE	4	SI
LUCERASTAT	3	SI
QUERCETIN	3	SI
THIAZOLIDINEDIONE	3	SI
DUVOGLUSTAT	2	SI
BAICALEIN	2	SI

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SI	148	Binding:148

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SI	3.2.1.10, 3.2.1.48	oligo-1,6-glucosidase, sucrose alpha-glucosidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SI	148

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

9 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)
MIGLUSTAT	4	SI
MIGALASTAT	4	SI
MIGLITOL	4	SI
ACARBOSE	4	SI
LUCERASTAT	3	SI
QUERCETIN	3	SI
THIAZOLIDINEDIONE	3	SI
DUVOGLUSTAT	2	SI
BAICALEIN	2	SI

Druggability pyramid

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

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

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05480761	PHASE4	TERMINATED	7-Day Trial of Sucraid for Alleviating CSID Symptoms in Subjects With Low, Moderate, and Normal Sucrase Levels
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05159115	Not specified	NOT_YET_RECRUITING	Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome
NCT05795049	Not specified	ACTIVE_NOT_RECRUITING	Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity
NCT06770907	Not specified	NOT_YET_RECRUITING	Genetic Carbohydrate Maldigestion As Model to Study Food Hypersensitivity Mechanism (WORK PACKAGE 2)
NCT07309601	Not specified	RECRUITING	Sucrase-Isomaltase (SI) Genes and Meal Load
NCT01914003	Not specified	COMPLETED	Congenital Sucrase-Isomaltase Deficiency (CSID) Genetic Prevalence Study (GPS)
NCT05045495	Not specified	COMPLETED	Adult Pilot Study for Reference Ranges and Optimal Cut-offs for the Sucrose Challenge Test and Sucrose Breath Test
NCT05375656	Not specified	COMPLETED	The Effect on Metabolism, Food Intake and Preferences of a Knockout Gene Variant Involved in Carbohydrate Metabolism
NCT05688826	Not specified	COMPLETED	The Effect of Sugar Load in IBS Patients Depending on Sucrase-isomaltase Genes