Congenital Sucrase-Isomaltase Deficiency

Mendelian MONDO:0009114 Pathograph 14 Gastrointestinal Disease

Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive brush-border disaccharidase deficiency caused by pathogenic SI variants. Reduced or absent sucrase-isomaltase activity impairs digestion of sucrose and, in some patients, starch-derived carbohydrates, producing carbohydrate malabsorption with osmotic diarrhea, bloating, and poor growth after dietary exposure.

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1
Inheritance
3
Pathophys.
5
Phenotypes
14
Pathograph
1
Genes
2
Treatments
7
References
1
Deep Research
👪

Inheritance

1
Autosomal Recessive HP:0000007
CSID is classically inherited as an autosomal recessive disorder caused by SI variants.
autosomal recessive inheritance
Show evidence (1 reference)
PMID:39128102 SUPPORT Human Clinical
"Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea."
Directly states the recessive inheritance pattern of CSID.
⚙

Pathophysiology

3
Brush-border sucrase-isomaltase deficiency
Enterocyte brush-border sucrase-isomaltase deficiency reduces hydrolysis of dietary sucrose and often impairs digestion of starch-derived carbohydrates, producing primary carbohydrate maldigestion.
enterocyte link
sucrase-isomaltase link
disaccharide metabolic process link ↓ DECREASED
sucrose alpha-glucosidase activity link ↓ DECREASED oligo-1,6-glucosidase activity link ↓ DECREASED
Downstream
Carbohydrate malabsorption and intestinal symptoms Failed sucrose and starch digestion leads to intestinal malabsorption and osmotic symptoms after carbohydrate exposure.
Reduced sucrase activity Loss of brush-border SI directly reduces sucrase activity.
Reduced or variable isomaltase activity SI deficiency variably reduces isomaltase activity, ranging from absent to almost normal.
Show evidence (2 references)
PMID:33772704 SUPPORT Human Clinical
"Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic disorder characterized by a deficiency of the sucrase-isomaltase (SI) enzyme complex within the brush border membrane of the small intestine."
Establishes that CSID reflects loss of the SI enzyme complex at the small-intestinal brush border.
PMID:38327254 SUPPORT Other
"Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene."
Shows that SI deficiency directly impairs digestion of sucrose and often starch.
Abnormal SI folding and apical trafficking
A subset of SI variants causes abnormal protein folding, increased turnover, endoplasmic reticulum retention, and impaired apical sorting, further reducing effective brush-border enzyme activity.
enterocyte link
sucrase-isomaltase link
protein folding link ⚠ ABNORMAL protein transport link ⚠ ABNORMAL
Downstream
Brush-border sucrase-isomaltase deficiency Misfolding and trafficking defects reduce apical SI availability at the enterocyte brush border.
Show evidence (3 references)
PMID:33772704 SUPPORT Human Clinical
"Mutations in the SI gene result in abnormal synthesis and/or incorrect transport of the SI enzyme."
Broad clinical abstract ties SI mutations to abnormal enzyme synthesis and transport.
PMID:11340066 SUPPORT In Vitro
"The impaired sorting profile to the apical membrane of human intestinal sucrase-isomaltase is the underlying cause in the pathogenesis of a novel phenotype of intestinal congenital sucrase-isomaltase deficiency."
Demonstrates that mutant SI can cause CSID through defective apical membrane sorting.
PMID:16543230 SUPPORT In Vitro
"Altogether, the combined effects of the C635R mutation on the turnover rate, function, polarized sorting, and detergent solubility of SI constitute a unique and novel pathomechanism of CSID."
Shows that altered folding, turnover, and polarized sorting together define a mechanistic CSID phenotype.
Carbohydrate malabsorption and intestinal symptoms
Undigested sucrose and starch-derived carbohydrates remain in the intestinal lumen, producing chronic intestinal malabsorption with osmotic diarrhea and associated nutritional consequences.
enterocyte link
carbohydrate metabolic process link ↓ DECREASED
Downstream
Osmotic Diarrhea Unabsorbed carbohydrate in the intestinal lumen drives osmotic diarrhea after sucrose or starch exposure.
Bloating Fermentation and malabsorption of undigested carbohydrate produce bloating and abdominal distention.
Abdominal Pain Abdominal pain is a common postprandial symptom in SI variant carriers and CSID families.
Failure to Thrive Chronic carbohydrate malabsorption can lead to poor growth and failure to thrive.
Malnutrition Persistent carbohydrate malabsorption and dietary intolerance can cause malnutrition.
Sucrose hydrogen breath test Sucrose malabsorption can be detected noninvasively by sucrose hydrogen breath testing.
Show evidence (2 references)
PMID:33972906 SUPPORT Human Clinical
"Congenital sucrase isomaltase deficiency (CSID) is an autosomal recessive disorder which leads to chronic intestinal malabsorption of nutrients from ingested starch and sucrose."
Directly links impaired starch and sucrose digestion to chronic intestinal malabsorption in CSID.
PMID:39128102 SUPPORT Human Clinical
"Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea."
Shows that carbohydrate malabsorption manifests clinically as chronic osmotic diarrhea.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Congenital Sucrase-Isomaltase Deficiency 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

5
Digestive 2
Malnutrition Malnutrition (HP:0004395)
Show evidence (1 reference)
PMID:33972906 SUPPORT Human Clinical
"Symptoms usually present after consumption of fruits, juices, grains, and starches, leading to failure to thrive and malnutrition."
Directly links symptomatic carbohydrate exposure in CSID to malnutrition.
Bloating Abdominal distention (HP:0003270)
Show evidence (2 references)
PMID:33972906 SUPPORT Human Clinical
"We present a case of a 50-year-old woman with persistent symptoms of bloating in spite of extensive evaluation and treatment."
Adult case report supports bloating as part of the CSID symptom spectrum.
PMID:39128102 SUPPORT Human Clinical
"bloating (22.2%)"
Family study reports bloating among symptomatic relatives with SI variants.
Constitutional 1
Abdominal Pain Abdominal pain (HP:0002027)
Show evidence (1 reference)
PMID:39128102 SUPPORT Human Clinical
"abdominal pain (37%)"
Family study reports abdominal pain as the most common complaint among symptomatic mutation-positive relatives.
Growth 1
Failure to Thrive Failure to thrive (HP:0001508)
Show evidence (1 reference)
PMID:24433566 SUPPORT Human Clinical
"three children, ranging from 16 to 19 months old, were referred to our tertiary children's hospital due to chronic watery diarrhea and failure to thrive."
Case series directly reports failure to thrive in children with CSID.
Other 1
Osmotic Diarrhea Osmotic diarrhea (HP:0033310)
Show evidence (2 references)
PMID:39128102 SUPPORT Human Clinical
"Congenital sucrase-isomaltase deficiency is an autosomal recessive inherited disaccharidase deficiency characterized by chronic osmotic diarrhea."
Directly supports osmotic diarrhea as a core CSID phenotype.
PMID:24433566 SUPPORT Human Clinical
"chronic watery diarrhea and failure to thrive."
Pediatric case series documents chronic watery diarrhea in children with CSID.
🧬

Genetic Associations

1
SI pathogenic variants (Causative)
Show evidence (2 references)
PMID:38327254 SUPPORT Other
"Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene."
Identifies SI mutation as the genetic cause of inherited sucrase-isomaltase deficiency.
PMID:33772704 SUPPORT Human Clinical
"Mutations in the SI gene result in abnormal synthesis and/or incorrect transport of the SI enzyme."
Links SI variants to the molecular defects in enzyme synthesis and trafficking that underlie CSID.
💊

Treatments

2
Sucrose- and starch-restricted diet
Action: dietary intervention MAXO:0000088
Dietary restriction of sucrose and, when needed, starch is first-line management and should be individualized to symptom tolerance.
Mechanism Target:
MODULATES Carbohydrate malabsorption and intestinal symptoms — Restricting sucrose and sometimes starch reduces the substrate load that drives malabsorption and osmotic symptoms.
Show evidence (1 reference)
PMID:38327254 SUPPORT Other
"Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms."
Review directly supports dietary substrate restriction as the mechanism-directed treatment for carbohydrate malabsorption.
Target Phenotypes: Osmotic diarrhea ↗ Abdominal distention ↗ Abdominal pain ↗ Failure to thrive ↗ Malnutrition ↗
Show evidence (2 references)
PMID:38327254 SUPPORT Other
"Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms."
Directly supports individualized sucrose restriction and, in some patients, starch restriction.
PMID:33972906 SUPPORT Human Clinical
"Treatment of CSID consists of limiting sucrose in diet and replacement therapy with sacrosidase."
Independent clinical report confirms dietary sucrose restriction as a core treatment.
Sacrosidase enzyme replacement therapy
Action: enzyme replacement therapy Ontology label: enzyme replacement or supplementation therapy MAXO:0000933
Agent: sacrosidase ↗
Oral sacrosidase can supplement deficient sucrase activity, although some patients still need ongoing starch restriction.
Mechanism Target:
RESTORES Brush-border sucrase-isomaltase deficiency — Sacrosidase supplements deficient sucrase activity and reduces sucrose-driven symptoms.
Show evidence (2 references)
PMID:33972906 SUPPORT Human Clinical
"Treatment of CSID consists of limiting sucrose in diet and replacement therapy with sacrosidase."
Clinical report supports sacrosidase replacement as enzyme supplementation for the brush-border sucrase deficiency.
PMID:39128102 SUPPORT Human Clinical
"Sacrosidase enzyme replacement was applied to 7 patients whose symptoms did not improve with dietary elimination. Clinical response was obtained after enzyme treatment."
Family study reports clinical response after sacrosidase, supporting the target-mechanism link.
Target Phenotypes: Osmotic diarrhea ↗ Abdominal distention ↗ Abdominal pain ↗ Failure to thrive ↗ Malnutrition ↗
Show evidence (3 references)
PMID:33972906 SUPPORT Human Clinical
"Treatment of CSID consists of limiting sucrose in diet and replacement therapy with sacrosidase."
Directly identifies sacrosidase replacement therapy as a treatment for CSID.
PMID:38327254 SUPPORT Other
"As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction."
Supports commercial sacrosidase use and shows that starch symptoms may persist despite enzyme therapy.
PMID:39128102 SUPPORT Human Clinical
"Sacrosidase enzyme replacement was applied to 7 patients whose symptoms did not improve with dietary elimination. Clinical response was obtained after enzyme treatment."
Family study reports clinical response after sacrosidase in patients whose symptoms persisted despite dietary elimination.
🔬

Biochemical Markers

3
Reduced sucrase activity (DECREASED)
Context: Reduced sucrase activity is the core measurable disaccharidase defect in CSID and reflects loss of SI catalytic function at the enterocyte brush border.
Pathograph Readouts
Readout Of Brush-border sucrase-isomaltase deficiency Negative Diagnostic
Reduced sucrase activity directly measures loss of brush-border SI catalytic function.
Show evidence (1 reference)
PMID:33772704 SUPPORT Human Clinical
"Patients with CSID generally have reduced sucrase activity"
Patient cohort background identifies reduced sucrase activity as the typical measurable CSID defect.
Show evidence (1 reference)
PMID:33772704 SUPPORT Human Clinical
"Patients with CSID generally have reduced sucrase activity"
Patient journey study summarizes reduced sucrase activity as the typical biochemical defect.
Reduced or variable isomaltase activity (DECREASED)
Context: Isomaltase activity in CSID is variable, ranging from absent to nearly normal, explaining why starch tolerance is more variable than sucrose intolerance.
Pathograph Readouts
Correlates With Brush-border sucrase-isomaltase deficiency Negative Diagnostic
Reduced or absent isomaltase activity is a variable biochemical readout of SI deficiency and helps explain variable starch intolerance.
Show evidence (1 reference)
PMID:33772704 SUPPORT Human Clinical
"levels of isomaltase activity range from absent to almost normal."
Patient cohort background supports variable isomaltase activity in CSID.
Show evidence (1 reference)
PMID:33772704 SUPPORT Human Clinical
"levels of isomaltase activity range from absent to almost normal."
Directly supports variable isomaltase activity among CSID patients.
Sucrose hydrogen breath test (INCREASED)
Context: Breath hydrogen after sucrose challenge is a noninvasive diagnostic readout of sucrose malabsorption when deficient sucrase-isomaltase leaves sucrose undigested in the intestinal lumen.
Pathograph Readouts
Readout Of Carbohydrate malabsorption and intestinal symptoms Positive Diagnostic
Increased breath hydrogen after sucrose challenge reports sucrose malabsorption downstream of SI deficiency.
Show evidence (1 reference)
PMID:33972906 SUPPORT Human Clinical
"Diagnosis is suspected on detailed patient history and confirmed by a disaccharidase assay using small intestinal biopsies or sucrose hydrogen breath test."
Clinical report identifies sucrose hydrogen breath testing as a diagnostic readout of CSID.
Show evidence (1 reference)
PMID:33972906 SUPPORT Human Clinical
"Diagnosis is suspected on detailed patient history and confirmed by a disaccharidase assay using small intestinal biopsies or sucrose hydrogen breath test."
The case report supports sucrose hydrogen breath testing as a diagnostic biochemical readout.
{ }

Source YAML

click to show 
name: Congenital Sucrase-Isomaltase Deficiency
creation_date: '2026-04-14T07:51:40Z'
updated_date: '2026-05-20T16:32:48Z'
category: Mendelian
synonyms:
- CSID
- congenital sucrose intolerance
- sucrase-isomaltase deficiency
description: >-
  Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive
  brush-border disaccharidase deficiency caused by pathogenic SI variants.
  Reduced or absent sucrase-isomaltase activity impairs digestion of sucrose
  and, in some patients, starch-derived carbohydrates, producing carbohydrate
  malabsorption with osmotic diarrhea, bloating, and poor growth after dietary
  exposure.
disease_term:
  preferred_term: congenital sucrase-isomaltase deficiency
  term:
    id: MONDO:0009114
    label: congenital sucrase-isomaltase deficiency
parents:
- Gastrointestinal Disease
inheritance:
- name: Autosomal Recessive
  inheritance_term:
    preferred_term: autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    CSID is classically inherited as an autosomal recessive disorder caused by
    SI variants.
  evidence:
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital sucrase-isomaltase deficiency is an autosomal recessive
      inherited disaccharidase deficiency characterized by chronic osmotic
      diarrhea.
    explanation: Directly states the recessive inheritance pattern of CSID.
genetic:
- name: SI pathogenic variants
  gene_term:
    preferred_term: sucrase-isomaltase
    term:
      id: hgnc:10856
      label: SI
  association: Causative
  features: >-
    SI variants can reduce catalytic activity directly or impair folding,
    processing, and apical delivery of the sucrase-isomaltase complex,
    producing variable loss of sucrase activity with more variable isomaltase
    deficiency.
  evidence:
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency
      in the ability to digest sucrose and potentially starch due to mutations
      in the sucrase-isomaltase (SI) gene.
    explanation: Identifies SI mutation as the genetic cause of inherited sucrase-isomaltase deficiency.
  - reference: PMID:33772704
    reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mutations in the SI gene result in abnormal synthesis and/or incorrect
      transport of the SI enzyme.
    explanation: Links SI variants to the molecular defects in enzyme synthesis and trafficking that underlie CSID.
pathophysiology:
- name: Brush-border sucrase-isomaltase deficiency
  description: >-
    Enterocyte brush-border sucrase-isomaltase deficiency reduces hydrolysis of
    dietary sucrose and often impairs digestion of starch-derived
    carbohydrates, producing primary carbohydrate maldigestion.
  genes:
  - preferred_term: sucrase-isomaltase
    term:
      id: hgnc:10856
      label: SI
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  molecular_functions:
  - preferred_term: sucrose alpha-glucosidase activity
    term:
      id: GO:0004575
      label: sucrose alpha-glucosidase activity
    modifier: DECREASED
  - preferred_term: oligo-1,6-glucosidase activity
    term:
      id: GO:0004574
      label: oligo-1,6-glucosidase activity
    modifier: DECREASED
  biological_processes:
  - preferred_term: disaccharide metabolic process
    term:
      id: GO:0005984
      label: disaccharide metabolic process
    modifier: DECREASED
  evidence:
  - reference: PMID:33772704
    reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic
      disorder characterized by a deficiency of the sucrase-isomaltase (SI)
      enzyme complex within the brush border membrane of the small intestine.
    explanation: Establishes that CSID reflects loss of the SI enzyme complex at the small-intestinal brush border.
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency
      in the ability to digest sucrose and potentially starch due to mutations
      in the sucrase-isomaltase (SI) gene.
    explanation: Shows that SI deficiency directly impairs digestion of sucrose and often starch.
  downstream:
  - target: Carbohydrate malabsorption and intestinal symptoms
    causal_link_type: DIRECT
    description: Failed sucrose and starch digestion leads to intestinal malabsorption and osmotic symptoms after carbohydrate exposure.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Congenital sucrase isomaltase deficiency (CSID) is an autosomal recessive
        disorder which leads to chronic intestinal malabsorption of nutrients
        from ingested starch and sucrose.
      explanation: Clinical report directly links SI deficiency to malabsorption of ingested starch and sucrose.
  - target: Reduced sucrase activity
    causal_link_type: DIRECT
    description: Loss of brush-border SI directly reduces sucrase activity.
    evidence:
    - reference: PMID:33772704
      reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients with CSID generally have reduced sucrase activity
      explanation: Patient cohort background supports reduced sucrase activity as a direct biochemical consequence of CSID.
  - target: Reduced or variable isomaltase activity
    causal_link_type: DIRECT
    description: SI deficiency variably reduces isomaltase activity, ranging from absent to almost normal.
    evidence:
    - reference: PMID:33772704
      reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        levels of isomaltase activity range from absent to almost normal.
      explanation: Patient cohort background supports variable isomaltase activity in CSID.
- name: Abnormal SI folding and apical trafficking
  description: >-
    A subset of SI variants causes abnormal protein folding, increased
    turnover, endoplasmic reticulum retention, and impaired apical sorting,
    further reducing effective brush-border enzyme activity.
  genes:
  - preferred_term: sucrase-isomaltase
    term:
      id: hgnc:10856
      label: SI
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  biological_processes:
  - preferred_term: protein folding
    term:
      id: GO:0006457
      label: protein folding
    modifier: ABNORMAL
  - preferred_term: protein transport
    term:
      id: GO:0015031
      label: protein transport
    modifier: ABNORMAL
  evidence:
  - reference: PMID:33772704
    reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Mutations in the SI gene result in abnormal synthesis and/or incorrect
      transport of the SI enzyme.
    explanation: Broad clinical abstract ties SI mutations to abnormal enzyme synthesis and transport.
  - reference: PMID:11340066
    reference_title: "Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The impaired sorting profile to the apical membrane of human intestinal
      sucrase-isomaltase is the underlying cause in the pathogenesis of a novel
      phenotype of intestinal congenital sucrase-isomaltase deficiency.
    explanation: Demonstrates that mutant SI can cause CSID through defective apical membrane sorting.
  - reference: PMID:16543230
    reference_title: "Altered folding, turnover, and polarized sorting act in concert to define a novel pathomechanism of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Altogether, the combined effects of the C635R mutation on the turnover
      rate, function, polarized sorting, and detergent solubility of SI
      constitute a unique and novel pathomechanism of CSID.
    explanation: Shows that altered folding, turnover, and polarized sorting together define a mechanistic CSID phenotype.
  downstream:
  - target: Brush-border sucrase-isomaltase deficiency
    causal_link_type: DIRECT
    description: Misfolding and trafficking defects reduce apical SI availability at the enterocyte brush border.
- name: Carbohydrate malabsorption and intestinal symptoms
  description: >-
    Undigested sucrose and starch-derived carbohydrates remain in the
    intestinal lumen, producing chronic intestinal malabsorption with osmotic
    diarrhea and associated nutritional consequences.
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  chemical_entities:
  - preferred_term: sucrose
    term:
      id: CHEBI:17992
      label: sucrose
    modifier: INCREASED
  - preferred_term: starch
    term:
      id: CHEBI:28017
      label: starch
    modifier: INCREASED
  biological_processes:
  - preferred_term: carbohydrate metabolic process
    term:
      id: GO:0005975
      label: carbohydrate metabolic process
    modifier: DECREASED
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital sucrase isomaltase deficiency (CSID) is an autosomal recessive
      disorder which leads to chronic intestinal malabsorption of nutrients
      from ingested starch and sucrose.
    explanation: Directly links impaired starch and sucrose digestion to chronic intestinal malabsorption in CSID.
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital sucrase-isomaltase deficiency is an autosomal recessive
      inherited disaccharidase deficiency characterized by chronic osmotic
      diarrhea.
    explanation: Shows that carbohydrate malabsorption manifests clinically as chronic osmotic diarrhea.
  downstream:
  - target: Osmotic Diarrhea
    causal_link_type: DIRECT
    description: Unabsorbed carbohydrate in the intestinal lumen drives osmotic diarrhea after sucrose or starch exposure.
    evidence:
    - reference: PMID:39128102
      reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Congenital sucrase-isomaltase deficiency is an autosomal recessive
        inherited disaccharidase deficiency characterized by chronic osmotic
        diarrhea.
      explanation: Human family study supports osmotic diarrhea as the clinical result of the disaccharidase deficiency.
  - target: Bloating
    causal_link_type: DIRECT
    description: Fermentation and malabsorption of undigested carbohydrate produce bloating and abdominal distention.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        We present a case of a 50-year-old woman with persistent symptoms of
        bloating in spite of extensive evaluation and treatment.
      explanation: Clinical report directly supports persistent bloating in CSID.
    - reference: PMID:39128102
      reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        abdominal pain (37%), gas irritability (33.3%), bloating (22.2%), and
        foul-smelling stools (18.5%).
      explanation: Family study reports bloating and gas-related symptoms among SI-variant carriers.
  - target: Abdominal Pain
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Carbohydrate malabsorption causes gas production, intestinal distention, and postprandial symptoms.
    description: Abdominal pain is a common postprandial symptom in SI variant carriers and CSID families.
    evidence:
    - reference: PMID:39128102
      reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        abdominal pain (37%), gas irritability (33.3%), bloating (22.2%), and
        foul-smelling stools (18.5%).
      explanation: Family study reports abdominal pain together with gas and bloating symptoms in mutation-positive relatives.
  - target: Failure to Thrive
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Chronic diarrhea and nutrient malabsorption impair growth.
    description: Chronic carbohydrate malabsorption can lead to poor growth and failure to thrive.
    evidence:
    - reference: PMID:24433566
      reference_title: "Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        three children, ranging from 16 to 19 months old, were referred to our
        tertiary children's hospital due to chronic watery diarrhea and failure
        to thrive.
      explanation: Pediatric case series links chronic diarrhea from CSID to failure to thrive.
  - target: Malnutrition
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Chronic dietary nutrient malabsorption limits effective nutrient uptake.
    description: Persistent carbohydrate malabsorption and dietary intolerance can cause malnutrition.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Symptoms usually present after consumption of fruits, juices, grains, and
        starches, leading to failure to thrive and malnutrition.
      explanation: Clinical report directly links carbohydrate-triggered CSID symptoms to malnutrition.
  - target: Sucrose hydrogen breath test
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Undigested sucrose reaches intestinal microbial metabolism.
    - Breath hydrogen increases after sucrose challenge when sucrose is malabsorbed.
    description: Sucrose malabsorption can be detected noninvasively by sucrose hydrogen breath testing.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Diagnosis is suspected on detailed patient history and confirmed by a
        disaccharidase assay using small intestinal biopsies or sucrose hydrogen
        breath test.
      explanation: Clinical report supports sucrose hydrogen breath testing as a diagnostic readout of CSID carbohydrate malabsorption.
phenotypes:
- name: Osmotic Diarrhea
  category: Gastrointestinal
  phenotype_term:
    preferred_term: osmotic diarrhea
    term:
      id: HP:0033310
      label: Osmotic diarrhea
  evidence:
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Congenital sucrase-isomaltase deficiency is an autosomal recessive
      inherited disaccharidase deficiency characterized by chronic osmotic
      diarrhea.
    explanation: Directly supports osmotic diarrhea as a core CSID phenotype.
  - reference: PMID:24433566
    reference_title: "Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      chronic watery diarrhea and failure to thrive.
    explanation: Pediatric case series documents chronic watery diarrhea in children with CSID.
- name: Failure to Thrive
  category: Growth
  phenotype_term:
    preferred_term: failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: PMID:24433566
    reference_title: "Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      three children, ranging from 16 to 19 months old, were referred to our
      tertiary children's hospital due to chronic watery diarrhea and failure
      to thrive.
    explanation: Case series directly reports failure to thrive in children with CSID.
- name: Malnutrition
  category: Nutritional
  phenotype_term:
    preferred_term: malnutrition
    term:
      id: HP:0004395
      label: Malnutrition
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Symptoms usually present after consumption of fruits, juices, grains, and
      starches, leading to failure to thrive and malnutrition.
    explanation: Directly links symptomatic carbohydrate exposure in CSID to malnutrition.
- name: Bloating
  category: Gastrointestinal
  phenotype_term:
    preferred_term: bloating
    term:
      id: HP:0003270
      label: Abdominal distention
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We present a case of a 50-year-old woman with persistent symptoms of
      bloating in spite of extensive evaluation and treatment.
    explanation: Adult case report supports bloating as part of the CSID symptom spectrum.
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      bloating (22.2%)
    explanation: Family study reports bloating among symptomatic relatives with SI variants.
- name: Abdominal Pain
  category: Gastrointestinal
  phenotype_term:
    preferred_term: abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      abdominal pain (37%)
    explanation: Family study reports abdominal pain as the most common complaint among symptomatic mutation-positive relatives.
biochemical:
- name: Reduced sucrase activity
  presence: DECREASED
  context: >-
    Reduced sucrase activity is the core measurable disaccharidase defect in
    CSID and reflects loss of SI catalytic function at the enterocyte brush
    border.
  readouts:
  - target: Brush-border sucrase-isomaltase deficiency
    relationship: READOUT_OF
    direction: NEGATIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Reduced sucrase activity directly measures loss of brush-border SI catalytic function.
    evidence:
    - reference: PMID:33772704
      reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients with CSID generally have reduced sucrase activity
      explanation: Patient cohort background identifies reduced sucrase activity as the typical measurable CSID defect.
  evidence:
  - reference: PMID:33772704
    reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with CSID generally have reduced sucrase activity
    explanation: Patient journey study summarizes reduced sucrase activity as the typical biochemical defect.
- name: Reduced or variable isomaltase activity
  presence: DECREASED
  context: >-
    Isomaltase activity in CSID is variable, ranging from absent to nearly
    normal, explaining why starch tolerance is more variable than sucrose
    intolerance.
  readouts:
  - target: Brush-border sucrase-isomaltase deficiency
    relationship: CORRELATES_WITH
    direction: NEGATIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Reduced or absent isomaltase activity is a variable biochemical readout of SI deficiency and helps explain variable starch intolerance.
    evidence:
    - reference: PMID:33772704
      reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        levels of isomaltase activity range from absent to almost normal.
      explanation: Patient cohort background supports variable isomaltase activity in CSID.
  evidence:
  - reference: PMID:33772704
    reference_title: "The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      levels of isomaltase activity range from absent to almost normal.
    explanation: Directly supports variable isomaltase activity among CSID patients.
- name: Sucrose hydrogen breath test
  presence: INCREASED
  context: >-
    Breath hydrogen after sucrose challenge is a noninvasive diagnostic readout
    of sucrose malabsorption when deficient sucrase-isomaltase leaves sucrose
    undigested in the intestinal lumen.
  biomarker_term:
    preferred_term: molecular hydrogen
    term:
      id: CHEBI:18276
      label: dihydrogen
  readouts:
  - target: Carbohydrate malabsorption and intestinal symptoms
    relationship: READOUT_OF
    direction: POSITIVE
    endpoint_context: DIAGNOSTIC
    interpretation: Increased breath hydrogen after sucrose challenge reports sucrose malabsorption downstream of SI deficiency.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Diagnosis is suspected on detailed patient history and confirmed by a
        disaccharidase assay using small intestinal biopsies or sucrose hydrogen
        breath test.
      explanation: Clinical report identifies sucrose hydrogen breath testing as a diagnostic readout of CSID.
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis is suspected on detailed patient history and confirmed by a
      disaccharidase assay using small intestinal biopsies or sucrose hydrogen
      breath test.
    explanation: The case report supports sucrose hydrogen breath testing as a diagnostic biochemical readout.
diagnosis:
- name: Duodenal disaccharidase assay
  description: >-
    Measurement of sucrase-isomaltase activity in duodenal mucosal tissue is
    the gold-standard diagnostic assay for SI deficiency.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  results: Reduced sucrase activity with variable isomaltase activity.
  evidence:
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Currently, disaccharidase assay on duodenal mucosal tissue homogenates is
      the gold standard in diagnosing SI deficiency.
    explanation: Clinical review identifies duodenal disaccharidase assay as the gold-standard diagnostic test.
- name: Noninvasive sucrose breath testing
  description: >-
    Noninvasive sucrose breath testing can support diagnosis by detecting
    sucrose malabsorption, although reviews note that additional validation is
    still needed.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  results: Increased breath hydrogen after sucrose challenge.
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Diagnosis is suspected on detailed patient history and confirmed by a
      disaccharidase assay using small intestinal biopsies or sucrose hydrogen
      breath test.
    explanation: Clinical report supports sucrose hydrogen breath testing as a diagnostic option.
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Other noninvasive diagnostic alternatives such as sucrose breath tests may
      be useful but require further validation.
    explanation: Review supports sucrose breath testing while noting that validation remains incomplete.
- name: Sucrose tolerance test
  description: >-
    Sucrose tolerance testing can show a flat glucose response and reproduce
    watery stool after sucrose challenge in affected children.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  results: Flat sucrose tolerance test with watery stool after sucrose challenge.
  evidence:
  - reference: PMID:24433566
    reference_title: "Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All three children had flat sucrose tolerance tests and began to have
      watery stool 2-4 hours after feeding sucrose test solution.
    explanation: Pediatric case series supports sucrose tolerance testing as a diagnostic clue in CSID.
treatments:
- name: Sucrose- and starch-restricted diet
  description: >-
    Dietary restriction of sucrose and, when needed, starch is first-line
    management and should be individualized to symptom tolerance.
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: MAXO:0000088
      label: dietary intervention
  evidence:
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Management of GSID is based on sucrose and potentially starch restriction
      tailored to the individual patients' tolerance and symptoms.
    explanation: Directly supports individualized sucrose restriction and, in some patients, starch restriction.
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment of CSID consists of limiting sucrose in diet and replacement
      therapy with sacrosidase.
    explanation: Independent clinical report confirms dietary sucrose restriction as a core treatment.
  target_mechanisms:
  - target: Carbohydrate malabsorption and intestinal symptoms
    treatment_effect: MODULATES
    description: Restricting sucrose and sometimes starch reduces the substrate load that drives malabsorption and osmotic symptoms.
    evidence:
    - reference: PMID:38327254
      reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Management of GSID is based on sucrose and potentially starch restriction
        tailored to the individual patients' tolerance and symptoms.
      explanation: Review directly supports dietary substrate restriction as the mechanism-directed treatment for carbohydrate malabsorption.
  target_phenotypes:
  - preferred_term: Osmotic diarrhea
    term:
      id: HP:0033310
      label: Osmotic diarrhea
  - preferred_term: Abdominal distention
    term:
      id: HP:0003270
      label: Abdominal distention
  - preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  - preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  - preferred_term: Malnutrition
    term:
      id: HP:0004395
      label: Malnutrition
- name: Sacrosidase enzyme replacement therapy
  description: >-
    Oral sacrosidase can supplement deficient sucrase activity, although some
    patients still need ongoing starch restriction.
  treatment_term:
    preferred_term: enzyme replacement therapy
    term:
      id: MAXO:0000933
      label: enzyme replacement or supplementation therapy
    therapeutic_agent:
    - preferred_term: sacrosidase
      term:
        id: NCIT:C66525
        label: Sacrosidase
  evidence:
  - reference: PMID:33972906
    reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Treatment of CSID consists of limiting sucrose in diet and replacement
      therapy with sacrosidase.
    explanation: Directly identifies sacrosidase replacement therapy as a treatment for CSID.
  - reference: PMID:38327254
    reference_title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      As this approach may be challenging, additional treatment with
      commercially available sacrosidase is available. However, some patients
      may require continued starch restriction.
    explanation: Supports commercial sacrosidase use and shows that starch symptoms may persist despite enzyme therapy.
  - reference: PMID:39128102
    reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Sacrosidase enzyme replacement was applied to 7 patients whose symptoms
      did not improve with dietary elimination. Clinical response was obtained
      after enzyme treatment.
    explanation: Family study reports clinical response after sacrosidase in patients whose symptoms persisted despite dietary elimination.
  target_mechanisms:
  - target: Brush-border sucrase-isomaltase deficiency
    treatment_effect: RESTORES
    description: Sacrosidase supplements deficient sucrase activity and reduces sucrose-driven symptoms.
    evidence:
    - reference: PMID:33972906
      reference_title: "Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Treatment of CSID consists of limiting sucrose in diet and replacement
        therapy with sacrosidase.
      explanation: Clinical report supports sacrosidase replacement as enzyme supplementation for the brush-border sucrase deficiency.
    - reference: PMID:39128102
      reference_title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Sacrosidase enzyme replacement was applied to 7 patients whose symptoms
        did not improve with dietary elimination. Clinical response was obtained
        after enzyme treatment.
      explanation: Family study reports clinical response after sacrosidase, supporting the target-mechanism link.
  target_phenotypes:
  - preferred_term: Osmotic diarrhea
    term:
      id: HP:0033310
      label: Osmotic diarrhea
  - preferred_term: Abdominal distention
    term:
      id: HP:0003270
      label: Abdominal distention
  - preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  - preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  - preferred_term: Malnutrition
    term:
      id: HP:0004395
      label: Malnutrition
references:
- reference: PMID:11340066
  title: Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder.
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:16543230
  title: Altered folding, turnover, and polarized sorting act in concert to define a novel pathomechanism of congenital sucrase-isomaltase deficiency.
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:24433566
  title: "Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children."
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:33772704
  title: The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency.
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:33972906
  title: Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female.
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:38327254
  title: "Genetic and acquired sucrase-isomaltase deficiency: A clinical review."
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
- reference: PMID:39128102
  title: "Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations."
  found_in:
  - Congenital_Sucrase-Isomaltase_Deficiency-deep-research-asta.md
  findings: []
📚

References & Deep Research

References

7
PMID:11340066
Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder.
No top-level findings curated for this source.
PMID:16543230
Altered folding, turnover, and polarized sorting act in concert to define a novel pathomechanism of congenital sucrase-isomaltase deficiency.
No top-level findings curated for this source.
PMID:24433566
Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children.
No top-level findings curated for this source.
PMID:33772704
The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency.
No top-level findings curated for this source.
PMID:33972906
Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female.
No top-level findings curated for this source.
PMID:38327254
Genetic and acquired sucrase-isomaltase deficiency: A clinical review.
No top-level findings curated for this source.
PMID:39128102
Congenital Sucrase-Isomaltase Deficiency: Same Mutation with Different Clinical Presentations.
No top-level findings curated for this source.

Deep Research

1
Asta ▸
Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Congenital Sucrase-Isomaltase Deficiency. Core disease mechanisms, molecul...
Asta Scientific Corpus Retrieval 15 citations 2026-04-14T00:43:29.710927

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Congenital Sucrase-Isomaltase Deficiency. Core disease mechanisms, molecul...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 15
  • Snippets retrieved: 20

Relevant Papers

[1] The genetics of monogenic intestinal epithelial disorders

  • Authors: Stephen J. Babcock, David Flores-Marin, Jay R. Thiagarajah
  • Year: 2022
  • Venue: Human Genetics
  • URL: https://www.semanticscholar.org/paper/9b0676b2e9805c377256b2b9e7f52547baf99670
  • DOI: 10.1007/s00439-022-02501-5
  • PMID: 36422736
  • PMCID: 10182130
  • Citations: 35
  • Influential citations: 3
  • Summary: The genetics, clinical presentation, and known pathophysiology for specific disorders, including a historical perspective of the field and relationship to other monogenic disorders of the intestine, are described.
  • Evidence snippets:
  • Snippet 1 (score: 0.669) > The sucrase-isomaltase (SI) gene, mapped to chromosome 3q26.1, codes for sucrase-isomaltase, a heterodimeric protein with two subunits, sucrase and isomaltase. Sucraseisomaltase is a type II transmembrane disaccharidase glycoprotein expressed in the intestinal brush border (Naim et al. 1988). Initially, the protein encoded by the SI gene is a precursor protein that is later cleaved by pancreatic proteases into sucrase and isomaltase. While sucrase hydrolyzes sucrose, isomaltase processes starch, isomaltose, and maltose. Therefore, patients with biallelic mutations of the SI gene are unable to metabolize these carbohydrates, and their consumption leads to a diet-induced diarrhea accompanied by different degrees of abdominal bloating and pain. This condition, congenital sucrase-isomaltase deficiency (CSID), was initially identified and described in the 1960s (Weijers et al. 1960). > There is still no clear consensus on the worldwide prevalence of congenital sucrase-isomaltase deficiency, due to the nonspecific nature of symptoms and variation in disease severity. Estimates place the mutation at around 0.2% in individuals of European descent, 5-10% in Greenland Innuits, and 3-7% in Canadian and Alaskan Innuits (Treem 2012). Four mutations are estimated to represent over 80% of CSID in European populations: p.Gly1073Asp, p.Val577Gly, p.Phe1745Cys, and p.Arg1124* (Gericke et al. 2017). A molecular and cellular analysis of 13 missense mutations has allowed for their classification into three major phenotypes based on whether protein trafficking, enzymatic activity, or lipid raft association is affected (Gericke et al. 2017). In general terms, however, these mutations result in some degree of improper targeting to the plasma membrane and a combined deficiency of both sucrase and isomaltase (Naim et al. 1988).
  • Snippet 2 (score: 0.405) > Although they are commonly linked and defined by altered intestinal epithelial function, CoDE disorders exhibit a wide variety of cell and tissue level pathophysiological mechanisms. Despite this heterogeneity some broad categories have emerged to classify specific genes. As the specific causative genes for many cases of non-acquired severe infantile-onset chronic diarrhea can now be established, it has become important to shift away from syndromic or clinically defined naming of disorders to more specific designation by affected gene (e.g., SPINT2 deficiency vs syndromic congenital sodium diarrhea). This is particularly relevant for current and future studies that aim to correlate specific mutations with phenotype, prognosis, and treatment. As with any attempt to classify such a heterogenous group of disorders there are specific genes/disorders that do not fit well in any one category. In some cases, such as the recently discovered WNT2B deficiency, this has allowed expansion or development of new categories. As new causative genes (e.g., PERCC1, UNC45A, AGR2) and new information on disease mechanisms continue to emerge, these categories will need ongoing revision and refinement. Disease can also be classified by other methods such as protein ontology (e.g., functional annotation) or clinical outcome (e.g., parenteral nutrition dependence). > Broadly, monogenic epithelial disorders can be classified into five major categories that comprise core modules of epithelial function. These are listed below (see also Fig. 1) and detailed descriptions of several disorders in each category follow: > • Epithelial transport

[2] Molecular Basis of Aberrant Apical Protein Transport in an Intestinal Enzyme Disorder*

  • Authors: N. Spodsberg, R. Jacob, Marwan Alfalah, K. Zimmer, H. Naim
  • Year: 2001
  • Venue: The Journal of Biological Chemistry
  • URL: https://www.semanticscholar.org/paper/839b8194012c3cf0aceebe90e4ee7cb53ae9b7da
  • DOI: 10.1074/jbc.C100219200
  • PMID: 11340066
  • Citations: 43
  • Influential citations: 1
  • Summary: The impaired sorting profile to the apical membrane of human intestinal sucrase-isomaltase is the underlying cause in the pathogenesis of a novel phenotype of intestinal congenital sucrase-isomaltase deficiency. Molecular characterization of this novel phenotype reveals a point mutation in the coding region of the sucrase-isomaltase (SI) gene that results in an amino acid substitution of a glutamine by arginine at residue 117 of the isomaltase subunit. This substitution is located in a domain...
  • Evidence snippets:
  • Snippet 1 (score: 0.585) > Investigating the molecular basis of naturally occurring mutant protein phenotypes in diseases constitutes therefore a powerful means to unravel the molecular mechanisms underlying intracellular protein transport and sorting. A small intestinal disorder directly associated with a folding mutant and defective intracellular protein transport is congenital sucrase-isomaltase defi-ciency (CSID). 1 CSID is an autosomal recessive disease that is characterized by an absent sucrase activity within the sucraseisomaltase (SI) enzyme complex, while the isomaltase activity can vary from absent to normal. The disease is clinically manifested as an osmotic-fermentative diarrhea upon ingestion of di-and oligosaccharides (4). Several phenotypes of the disease have been characterized on the basis of cellular mislocalization or aberrant function of the SI mutant protein. SI is a type II membrane-bound glycoprotein of the intestinal brush border comprising two strongly homologous subunits, sucrase and isomaltase (5)(6)(7)(8). These two domains originate from a large polypeptide precursor, pro-SI, by tryptic cleavage occurring in the intestinal lumen and ultimately maintain a strong association through noncovalent ionic interactions (9,10). This enzyme complex is a heavily N-and O-glycosylated protein (10). > Particularly O-glycosylation is critical for targeting of SI to the apical membrane through direct association in detergent-insoluble lipid rafts (11). > In this paper we describe a novel phenotype of CSID and the corresponding mutation, which results in a random distribution of the SI protein at the apical and basolateral membrane. Here a point mutation, an adenine to glutamine at nucleotide 412 in the coding region of the isomaltase subunit, results in a substitution of glutamine to arginine at amino acid residue 117. Defects in polarized protein sorting implicated in the pathogenesis of diseases have been rarely observed, perhaps because such defects have lethal consequences during early stages of development.
  • Snippet 2 (score: 0.447) > The impaired sorting profile to the apical membrane of human intestinal sucrase-isomaltase is the underlying cause in the pathogenesis of a novel phenotype of intestinal congenital sucrase-isomaltase deficiency. Molecular characterization of this novel phenotype reveals a point mutation in the coding region of the sucraseisomaltase (SI) gene that results in an amino acid substitution of a glutamine by arginine at residue 117 of the isomaltase subunit. This substitution is located in a domain revealing features of a trefoil motif or a P-domain in immediate vicinity of the heavily O-glycosylated stalk domain. Expression of the mutant SI phenotype in epithelial Madin-Darby canine kidney cells reveals a randomly targeted SI protein to the apical and basolateral membranes confirming an exclusive role of the Q117R mutation in generating this phenotype. Unlike wild type SI, the mutant protein is completely extractable with Triton X-100 despite the presence of O-glycans that serve in the wild type protein as an apical sorting signal and are required for the association of SI with detergent-insoluble lipid microdomains. Obviously the O-glycans are not adequately recognized in the context of the mutant SI, most likely due to altered folding of the Pdomain that ultimately affects the access of the O-glycans to a putative sorting element. > The composition and function of the plasma membrane of polarized cells are maintained by a complex intracellular traffic moving cell surface glycoproteins between organelles. This requires the recognition and sorting of different classes of proteins not only during biosynthesis, but also during distributive events to the diverse cellular compartments (1). Oftentimes altered and defective intracellular trafficking of proteins due to single point or deletion mutations in the coding region of the gene result in pathological disorders (2,3). Investigating the molecular basis of naturally occurring mutant protein phenotypes in diseases constitutes therefore a powerful means to unravel the molecular mechanisms underlying intracellular protein transport and sorting.

[3] Altered Folding, Turnover, and Polarized Sorting Act in Concert to Define a Novel Pathomechanism of Congenital Sucrase-Isomaltase Deficiency*

  • Authors: M. Keiser, Marwan Alfalah, M. Pröpsting, D. Castelletti, H. Naim
  • Year: 2006
  • Venue: Journal of Biological Chemistry
  • URL: https://www.semanticscholar.org/paper/d9d6b2e9f7396a8f3b728c64ff1a1af829c29441
  • DOI: 10.1074/jbc.M513631200
  • PMID: 16543230
  • Citations: 26
  • Influential citations: 1
  • Summary: The combined effects of the C635R mutation on the turnover rate, function, polarized sorting, and detergent solubility of SI constitute a unique and novel pathomechanism of CSID.
  • Evidence snippets:
  • Snippet 1 (score: 0.543) > The utilization of misfolding-related diseases has proven to be invaluable in dissection of the molecular mechanisms of protein transport and has unraveled several intriguing cell biological phenomena, such as in cases of congenital sucrase-isomaltase deficiency (CSID). 3 This intestinal autosomal recessive disorder is characterized by the absence of the sucrase and most of the maltase digestive activity within the sucraseisomaltase (SI) enzyme complex. The isomaltase activity varies from absent to normal (1). Clinically, the disease is manifested as an osmotic-fermentative diarrhea upon ingestion of disaccharides and oligosaccharides (2). Analysis of this disorder at the molecular and subcellular levels has unraveled a number of phenotypes of CSID, which are characterized by perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI (3)(4)(5). A few examples have been also reported, in which the misfolded protein products may escape the quality control system, instead of being either degraded or retained in the ER. A mutation at the position 620 of SI (L620P), for example, has been identified as one of the possible genetic modifications occurring in the CSID (6). Although this mutant is mainly found to be localized in the ER, it can be at least partially expressed also on the cell surface. Moreover, Propsting et al. (7) reported on the Q1098P mutation of SI causing an incomplete folding of the protein, which is however insufficient to trigger the complete protein block into the ER. In fact, the protein can exit the ER and reach the cis-Golgi compartment eluding partially the quality control in the ER. > SI is a type II transmembrane glycoprotein of two highly homologous subunits, sucrase and isomaltase (5,8), that is expressed at the intestine brush-border membrane, where it serves as a catalyst for the cleavage of sugar and starch (9,10).
  • Snippet 2 (score: 0.462) > Altered Folding, Turnover, and Polarized Sorting Act in Concert to Define a Novel Pathomechanism of Congenital Sucrase-Isomaltase Deficiency*

[4] Congenital sucrase–isomaltase deficiency: A case report

  • Authors: Rita Santos-Silva, M. Tavares, E. Trindade, J. Amil-Dias
  • Year: 2014
  • Venue: GE Portuguese Journal of Gastroenterology
  • URL: https://www.semanticscholar.org/paper/8d3a3b0515f905d79731cc2fece2183699464bbf
  • DOI: 10.1016/J.JPGE.2014.07.004
  • Citations: 2
  • Summary: The case of a six-month-old male infant admitted for chronic profuse diarrhea and failure to thrive that began after food diversification showed that he had CSID and the therapeutic option was the addition of baker's yeast to the diet which was followed by complete resolution of symptoms and excellent weight recovery.
  • Evidence snippets:
  • Snippet 1 (score: 0.520) > Congenital sucrase–isomaltase deficiency: A case report
  • Snippet 2 (score: 0.431) > Congenital sucrase---isomaltase deficiency (OMIM #222900) is caused by homozygous or compound heterozygous mutation in the SI gene, which encodes sucrase---isomaltase on chromosome 3q26. > Sucrase---isomaltase is an enterocyte-specific small intestine brush-border membrane disaccharidase. It is required for hydrolysis of sucrose and some starches. Upon ingestion of disaccharides and oligosaccharides, the failure to breakdown sucrose into fructose and glucose results in osmotic-fermentative diarrhea. > CSID is the most common congenital disorder of carbohydrate metabolism. Its estimated prevalence in North America and Europe ranges from 0.05% to 0.2%, 1 although this diagnosis is believed to be frequently missed. > Onset usually occurs during infancy after weaning from breast milk or lactose-only formula onto foods containing sucrose or starch. Clinical manifestations include osmotic-fermentative diarrhea, abdominal distension and discomfort, flatulence, vomiting and diaper rash. 2 Severe symptoms may lead to failure to thrive, dehydration and malnutrition. Adolescents and adults may present with signs of 'irritable bowel syndrome'. Carbohydrates result in a dose-dependent acceleration of colonic transit 3 and therefore symptoms may only occur with the ingestion of large amounts of sucrose. 2 CSID is a heterogeneous disorder. Identified mutations lead to a range of posttranslational defects resulting in an absence of sucrase activity and varying degrees of isomaltase deficiency. Heterozygotes have intermediate enzyme values and are usually asymptomatic in adulthood, but may have mild symptoms in infancy. > Several tests can be used to diagnose CSID, with measurement of intestinal disaccharides' activities being the gold standard. 2 It will show complete or almost complete lack of sucrase/isomaltase activity with normal lactase activity and normal villous architecture. > The hydrogen breath test is a non-invasive method for detecting carbohydrate malabsor

[5] The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency

  • Authors: Heather Smith, B. Romero, E. Flood, A. Boney
  • Year: 2021
  • Venue: Quality of Life Research
  • URL: https://www.semanticscholar.org/paper/f228fbd0c2786b440fbc2a8fa4d1f9daa487be69
  • DOI: 10.1007/s11136-021-02819-z
  • PMID: 33772704
  • PMCID: 8298246
  • Citations: 13
  • Influential citations: 1
  • Summary: Patients with CSID reported considerable improvement in symptoms and health-related quality of life (HRQL), yet symptoms persist that continue to affect daily life, indicating areas of potential unmet need.
  • Evidence snippets:
  • Snippet 1 (score: 0.485) > The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency

[6] Congenital Sucrase–Isomaltase Deficiency: Same Mutation with Different Clinical Presentations

  • Authors: Fatma İssi Irlayıcı, Burcu Güven, Murat Çakır
  • Year: 2024
  • Venue: The Turkish Journal of Gastroenterology
  • URL: https://www.semanticscholar.org/paper/8409fe40c8e26f051972ac3162dec0d2b6a75c36
  • DOI: 10.5152/tjg.2024.23250
  • PMID: 39128102
  • PMCID: 11114242
  • Citations: 1
  • Summary: Despite its autosomal recessive inheritance, congenital sucrase–isomaltase deficiency can also be symptomatic in heterozygous individuals, and further studies are required to clarify the genotype–phenotype relationship and management of the disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.466) > Congenital Sucrase–Isomaltase Deficiency: Same Mutation with Different Clinical Presentations

[7] Congenital Diarrheal Disorders: An Updated Diagnostic Approach

  • Authors: G. Terrin, R. Tomaiuolo, A. Passariello, A. Elce, F. Amato et al.
  • Year: 2012
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/7cae68c68d2fabcd2ee0726efbbebe14095527ed
  • DOI: 10.3390/ijms13044168
  • PMID: 22605972
  • PMCID: 3344208
  • Citations: 69
  • Influential citations: 3
  • Summary: This work reviews CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.
  • Evidence snippets:
  • Snippet 1 (score: 0.460) > This group can be further divided in various subgroups on the basis of the specific gene defect. The first subgroup includes the deficiency of brush border enzymes, and in particular congenital LD due to mutations within the gene encoding the protein with either lactase and phlorizin hydrolase activities [26]; congenital SID, due to mutations in the gene encoding the protein with both sucrase and isomaltase activity [8], and congenital maltase-glucoamylase deficiency (MGD), putatively due to the maltase-glucoamylase (MGAM) gene defect [8], even if some patients with the disease do not bear pathogenetic mutations in such gene. In fact, cases in which MGD was associated to the deficiency of other brush border enzymes were described, and it has been postulated that a pleiotropic regulator factor of such genes may be impaired in these patients [27]. > A large subgroup derives from mutations of genes encoding members of the super-family of solute carriers (SLC). These genes are structurally related and originated by mechanisms of duplication, but despite the homology of the gene sequence and the similarity of the protein architecture, the clinical picture and the outcome of these CDDs is heterogeneous. Most proteins encoded by SLC genes are expressed at intestinal level, thus the disease typically appears with diarrhea and selective malabsorption. In other cases the carrier is expressed also in other organs (i.e., the aminoacid transporter involved in LPI is expressed also in other tissues) and thus the disease could involves other organs or be systemic [7]. For some CDDs disease-genes are still unknown or more genes may be involved. For example, the disease gene for fructose malabsorption is still undefined [8,17,28]. There remains insufficient evidence that glucose transporter (GLUT) 5 represents the main fructose facilitative carrier in the intestine [17,28]. Recent studies have identified GLUT7 as a high affinity glucose and fructose carrier on the brush border membrane of the enterocyte located in the distal intestine.

[8] Diagnosing and Treating Intolerance to Carbohydrates in Children

  • Authors: R. Berni Canani, V. Pezzella, Antonio Amoroso, T. Cozzolino, C. di Scala et al.
  • Year: 2016
  • Venue: Nutrients
  • URL: https://www.semanticscholar.org/paper/a5fdd2fdf0f680a72d998224c244d8854d4ffa4f
  • DOI: 10.3390/nu8030157
  • PMID: 26978392
  • PMCID: 4808885
  • Citations: 65
  • Influential citations: 1
  • Summary: The most up-to-date research on intolerance to carbohydrates is examined, controversies relating to the diagnostic approach are discussed, including the role of molecular analysis, and new insights into modern management in the pediatric age are provided.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Congenital sucrose-isomaltase deficiency (CSID, OMIM #222900) is a rare autosomal recessive inherited disease of the small intestine resulting from genetic mutations in sucrase-isomaltase, an enzyme complex responsible for catalyzing the hydrolysis of dietary sucrose and starch [17]. Decreased or absent sucrase and/or isomaltase enzymatic activity has been found in patients with CSID, and investigations at the subcellular and molecular levels in intestinal biopsy specimens have led to the description of several phenotypes, differing in transport efficiency, processing, and sorting of the protein, which result in impaired physiologic functions [17][18][19][20]. In addition to the degree of enzyme deficiency, the appearance of overt clinical manifestations of CSID is partially determined by the amount of sugar and starch consumed [21]. The prevalence in the European population has been estimated at 1 in 5000, but it is higher among the indigenous populations of Alaska, Greenland, and Canada [22]. Gastrointestinal symptoms usually begin after an infant is weaned off breast milk and is first exposed to sucrose and starch [23]. Failure to absorb dietary disaccharides and starch has implications for the absorption of other nutrients and the hormonal regulation of gastrointestinal function. For these reasons, patients with CSID are at risk for chronic malnutrition and failure to thrive. In many cases, the symptoms of CSID are more severe in infants than in adults. It has been suggested that an increased susceptibility to symptoms in infants is related to a shorter length of the small intestine. Although intestinal biopsy is still adopted in many
  • Snippet 2 (score: 0.415) > Congenital sucrose-isomaltase deficiency (CSID, OMIM #222900) is a rare autosomal recessive inherited disease of the small intestine resulting from genetic mutations in sucrase-isomaltase, an enzyme complex responsible for catalyzing the hydrolysis of dietary sucrose and starch [17]. Decreased or absent sucrase and/or isomaltase enzymatic activity has been found in patients with CSID, and investigations at the subcellular and molecular levels in intestinal biopsy specimens have led to the description of several phenotypes, differing in transport efficiency, processing, and sorting of the protein, which result in impaired physiologic functions [17][18][19][20]. In addition to the degree of enzyme deficiency, the appearance of overt clinical manifestations of CSID is partially determined by the amount of sugar and starch consumed [21]. The prevalence in the European population has been estimated at 1 in 5000, but it is higher among the indigenous populations of Alaska, Greenland, and Canada [22]. Gastrointestinal symptoms usually begin after an infant is weaned off breast milk and is first exposed to sucrose and starch [23]. Failure to absorb dietary disaccharides and starch has implications for the absorption of other nutrients and the hormonal regulation of gastrointestinal function. For these reasons, patients with CSID are at risk for chronic malnutrition and failure to thrive. In many cases, the symptoms of CSID are more severe in infants than in adults. It has been suggested that an increased susceptibility to symptoms in infants is related to a shorter length of the small intestine. Although intestinal biopsy is still adopted in many tertiary centers for CSID diagnosis, genetic testing is now widely available. Molecular genetics has become helpful for obtaining an early and unequivocal diagnosis in infants with chronic diarrhea due to any of a variety of different disorders, thus permitting rapid and targeted therapeutic strategies and reducing repetitive, invasive, and expensive procedures. At least 80% of CSID patients have one of four common mutations [22,24].

[9] Our Cases with Sucrase Isomaltase Deficiency

  • Authors: Miray Karakoyun, Erhan Kilicoglu, Y. Şahan, M. Baran, F. Ünal et al.
  • Year: 2015
  • Venue: Journal of Gastrointestinal and Digestive System
  • URL: https://www.semanticscholar.org/paper/aced4166c3fe683d3c5f6f19bfaa0451ca588d2f
  • DOI: 10.4172/2161-069X.1000354
  • Citations: 7
  • Summary: It is suggested that sucrase isomaltase deficiency should be considered in pediatric patients presenting with chronic watery diarrhea, due to the actual prevalence of the disease in Turkey is unknown.
  • Evidence snippets:
  • Snippet 1 (score: 0.444) > Our Cases with Sucrase Isomaltase Deficiency

[10] Naturally occurring mutations in intestinal sucrase-isomaltase provide evidence for the existence of an intracellular sorting signal in the isomaltase subunit [published erratum appears in J Cell Biol 1991 Dec;115(5):following 1473]

  • Authors: Jack A.M. Fransen, H.-P. Hauri, L. Ginsel, H. Naim
  • Year: 1991
  • Venue: The Journal of Cell Biology
  • URL: https://www.semanticscholar.org/paper/9bc9d26e3d7b6897f94fa25fa487cca783f30855
  • DOI: 10.1083/JCB.115.1.45
  • PMID: 1717481
  • PMCID: 2289914
  • Citations: 60
  • Summary: It is concluded that structural features in the isomaltase region of pro-SI are required for transport and sorting of the sucrase-isomalase complex.
  • Evidence snippets:
  • Snippet 1 (score: 0.432) > Recent studies in an intestinal epithelial cell line, Caco-2, have suggested that proteins destined for the microvillar membrane are selectively sorted before their transport to that membrane (Hauri, 1988;Matter et al., 1990) ; basolateral proteins are on the other hand nonselectively sorted and reach their final destination by a default pathway (Rindler and Traber, 1988) . Although the molecular mechanisms underlying these events have not been unraveled yet, an attractive hypothesis is that selective sorting is accomplished by cellular recognition elements that recognize sorting signals or specific structural motifs in the mature protein and interact with them in a ligand/receptor fashion . Proteins that are not identified by these recognition elements are then translocated to the basolateral membrane . The nature and/or structure of putative sorting signals are unknown . > In accordance with this hypothesis, it is conceivable that slight alterations in the sorting signal of an otherwise sorted protein will disrupt its interaction with signal recognition elements leading to a protein that operates by default. Naturally occurring mutant phenotypes of proteins that are missorted have been rarely observed . > We have presented in this paper two novel phenotypes (phenotype IV and phenotype V) of sucrase-isomaltase in congenital sucrase-isomaltase deficiency (CSID) . One of these, phenotype IV, is the first identification of a protein that is missorted to the basolateral membrane in a naturally occurring mutant phenotype. > Figure 11. (a) Biosynthesis and maturation of aminopeptidase N (ApN) in intestinal mucosa of patient II . Biopsies were cultured for the indicated time periods in the presence of [35S]methionine. Immunoprecipitation was carried out with a single mAb against ApN from homogenates (H) or the culture medium (M) . One of two identical immunoprecipitates was treated with endo H to probe for high-mannose and complex-glycosylated forms.

[11] Congenital sucrase-isomaltase deficiency

  • Authors: W. Chey, Brooks D. Cash, A. Lembo, Daksesh B. Patel, Kate Scarlata
  • Year: 2020
  • Venue: Definitions
  • URL: https://www.semanticscholar.org/paper/76f5b736ef9ba6e0591490905b4f842bd24136b1
  • DOI: 10.1007/978-3-540-29676-8_8998
  • Citations: 78
  • Influential citations: 2
  • Summary: An autosomal recessive genetic disorder caused by mutations in the SI gene, encoding sucrase-isomaltase, intestinal, characterized by malabsorption and osmotic diarrhea.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > Congenital sucrase-isomaltase deficiency

[12] Sucrase-Isomaltase Deficiency Causing Persistent Bloating and Diarrhea in an Adult Female

  • Authors: Varsha Chiruvella, A. Cheema, H. Arshad, Jacqueline Chan, J. Yap
  • Year: 2021
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/5cd814695789b24a10c6beb6bc6b1725e61fc682
  • DOI: 10.7759/cureus.14349
  • PMID: 33972906
  • PMCID: 8105231
  • Citations: 7
  • Summary: A 50-year-old woman with persistent symptoms of bloating in spite of extensive evaluation and treatment is presented with CSID, an autosomal recessive disorder which leads to chronic intestinal malabsorption of nutrients from ingested starch and sucrose.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > Congenital sucrase isomaltase deficiency (CSID), also known as genetic sucrase deficiency, is a multifaceted intestinal malabsorption disorder with an autosomal recessive mutation in the sucrase-isomaltase (SI) gene on chromosome 3 (3q25-q26). Sucrase-isomaltase is a type II membrane enzyme complex and member of the disaccharidase family required for the breakdown of α-glycosidic linkages in sucrose and maltose. When this enzyme complex is deficient, nutrients from ingested starch and sucrose cannot be absorbed sufficiently. Infants and young children generally develop symptoms such as explosive watery diarrhea, abdominal distension, colic, and dehydration after consumption of fruits, juices, grains, modified milk formulas, and starches. These dietary symptoms reduce an individual's absorption of essential dietary nutrients and cause malnutrition. In infants and children, this commonly manifests as failure to gain appropriate weight and height and presents as low body weight in adults. However, starch intolerance often disappears during childhood, and symptoms of sucrose intolerance usually improve as the affected child ages [1]. A confirmatory CSID diagnosis can be made by a disaccharidase assay using a small bowel tissue biopsy or sucrose breath testing. Treatment for the condition consists of a combination approach of diet modification limiting sucrose and sucrase enzyme replacement therapy with sacrosidase, obtained from baker's yeast and glycerin, which is the only Food and Drug Administration (FDA) approved treatment for this condition [2]. However, due to CSID's nonspecific symptoms diagnosis is usually delayed. Prevalence of CSID may also be underrecognized due to overlapping presentation with other gastrointestinal (GI) conditions such as irritable bowel syndrome (IBS) and celiac disease, so the condition may be of greater clinical significance than previously suspected [3].

[13] Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children

  • Authors: L. Geng, Ding-You Li, Wen-ji Ou, Qunying Yang, Tiefu Fang et al.
  • Year: 2014
  • Venue: BMC Pediatrics
  • URL: https://www.semanticscholar.org/paper/cf422f5ac242252a3153f89b7d7d8fe587283ad4
  • DOI: 10.1186/1471-2431-14-11
  • PMID: 24433566
  • PMCID: 3927221
  • Citations: 10
  • Influential citations: 1
  • Summary: This is the first case series of CSID in Chinese children and the diagnosis can be made based on clinical suspicion and sucrose tolerance test and no children developed watery stools up to 4 hours after feeding glucose test solution.
  • Evidence snippets:
  • Snippet 1 (score: 0.419) > Congenital sucrase-isomaltase deficiency: an under-diagnosed disease in Chinese children

[14] Histopathology of intestinal villi in neonatal and paediatric age: main features with clinical correlation - Part I

  • Authors: Chiara Rossi, Gloria Simoncelli, Giovanni Arpa, A. Stracuzzi, P. Parente et al.
  • Year: 2021
  • Venue: Pathologica
  • URL: https://www.semanticscholar.org/paper/05ec008cc8fb5e3aa285fa656fe0bd632eb90ea6
  • DOI: 10.32074/1591-951X-337
  • PMID: 34856604
  • PMCID: 9040547
  • Citations: 4
  • Summary: This review aims to provide a comprehensive histopathological summary of paediatric small bowel alteration and their differential diagnoses with a reference to the main clinical aspects required for appropriate interpretation.
  • Evidence snippets:
  • Snippet 1 (score: 0.410) > Several congenital disorders of substrate digestion, absorption and transport have been described. The main subgroups included in this family are: i) disaccharidase deficiencies, ii) lipid trafficking disorders, and iii) ion and nutrient transport deficiencies. Apart from fat processing disorders, which may show rela-tively specific histopathologic features, small bowel histology of these enteropathies is generally normal or near normal and genetic analysis is required for their definitive diagnosis. Congenital disaccharidase deficiencies are rare, genetically determined entities, that comprise: i) congenital lactase deficiency, ii) sucrase-isomaltase deficiency, iii) maltase-glucoamylase deficiency, and iv) trehalase deficiency. Lactase-phlorizin hydrolase, sucrase-isomaltase, maltase-glucoamylase and trehalase are enzymes responsible for degradation of milk lactose, sucrose, starch, and mushroom trehalose, respectively. These enzymes are expressed on the brush border of villous absorptive cells in a time-dependent pattern (e.g. lactase is mainly expressed in neonates). Disaccharidase deficiencies cause a severe, osmotic-type diarrhoea in children. Importantly, small bowel mucosa looks histologically normal. Congenital disaccharidase disorders should be distinguished from secondary disaccharidase defects due to mucosal damage occurring in various enteropathies of different aetiology (e.g. coeliac or Crohn's disease) and from other disorder leading to carbohydrate malabsorption such as congenital fructose malabsorption, due to mutation in GLUT5 gene, which encodes for a hexose transporter at enterocyte basolateral membrane. Congenital lipid trafficking disorders are characterized by primary defects in lipid transport within absorptive cells, resulting in fat malabsorption, steatorrhoea, failure to thrive and various neurologic symptoms in neonates. They include i) abetalipoproteinaemia, ii) hypolipoproteinaemia, and iii) Anderson disease. They

[15] Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

  • Authors: T. Danialifar, B. Chumpitazi, Devendra I Mehta, C. Di Lorenzo
  • Year: 2024
  • Venue: Journal of pediatric gastroenterology and nutrition
  • URL: https://www.semanticscholar.org/paper/7180bb4ab8b870683b89c2aebf30234b9a600ba8
  • DOI: 10.1002/jpn3.12151
  • PMID: 38327254
  • Citations: 26
  • Influential citations: 3
  • Summary: Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms, and additional treatment with commercially available sacrosidase is available, however, some patients may require continued starch restriction.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

Notes

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  • No synthesis or second-stage model call is performed.