Sucrase-Isomaltase Deficiency

By Kristin Dermody & Sara Murkowski

Sucrase-Isomaltase: Digestive Function 

n   Brush border disaccharidase

n   Required for hydrolysis of dietary sucrose

n   Catalyzes degradation of sucrose to monosaccharides for intestinal absorption

n   The digestive tract is can only absorp CHO’s in form of monosaccharides

n   Let’s take a moment to talk carbs…

CHO 101

n    Monosaccharides

n    Glucose, Fructose, Galactose

n    Readily absorbed across intestinal lumen

n    Disaccharides

n    Sucrose (glucose+fructose)

n    Lactose (glucose+galactose)

n    Maltose (glucose+glucose)

n    Starches (polysaccharides)

n    Contain 15-30% amylose, 70-85% amylopectin

CHO Digestion and Absorption

In lumen

n     Starch à maltose + maltriose + á-limit dextrins

n      Amylase

At brush-border

n     Maltose/maltriose à glucose

n      Glucoamylase (maltase)

n      Sucrase-isomaltase

n     á-limit dextrins à glucose

n      Sucrase-isomaltase

n     Sucrose à glucose + fructose

n      Sucrase-isomaltase

n     Lactose à glucose + galactose

n      Lactase

Congenital Sucrase Isomaltase Deficiency

n    An autosomal recessive human intestinal disorder

n    Characterized by fermentative diarrhea, abdominal pain and cramps upon ingestion of sucrose, some starches

n    Symptoms are consequence of absent/drastically reduced enzymatic activities of the sucrase-isomaltase complex

Multiple Forms of CSID

n   5 Distinct phenotypes documented

n   Complete lack of sucrase in all forms

n   Isomaltase activity varies depending on phenotype

n   Genetic variability likely cause for large range in severity of symptoms among affected patients

Incidence and Prevalence of CSID

n    The congenital absence of digestive enzymes is a rare disorder affecting about 0.2% North Americans

n    Due to varying severity of disease, definite incidence and prevalence is uncertain

n    CSID most common among congenital digestive enzyme deficiencies

n    CSID is most common in Canadian Inuits and natives of Greenland.

Pathophysiology of CSID

n   Rare inborn error of metabolism

n   Results from mutation of sucrase-isomaltase at cellular level

  Mutations prevent completion & transport of enzyme to brush border enterocytes

n   SI deficiency results in increased luminal disaccharides and consequent osmotic diarrhea

What are the Symptoms?

n   Watery diarrhea

n   Abdominal cramps

n   Flatulence

n   Bloating

n   Occasional Vomiting

n   Highly similar to lactose intolerance!

Symptoms are Conditional

n   Severity of Sx’s dependent on:

n   Distinct phenotype of CSID

n   Quantity of sugar consumed

n   Colonic bacterial activity

n   Absorptive capacity of colon

n   Rate of gastric emptying

n   Small bowel transit time

n   Symptoms typically more severe in infants than adults

n   More rapid passage of CHO content through small intestine and colon

n   Greater degree of malabsorption in infants than adults

Clinical Manifestations

n   Severe chronic diarrhea

n   Lethargy

n   Fatigue

n   Failure to thrive

Nutritional Implications

n   Malabsorption of CHO

n   Weight loss

n   Dehydration

n   Electrolyte imbalance

n   Poor POs

n   Ultimately, malnutrition!

Detection & Diagnosis of CSID

n   First onset of symptoms generally at weaning from breast milk

n   Sucrose and starch is introduced in form of fruit juices and solid foods

n   Early observations noted in infants fed modified milk formulas with sucrose or polycose

Diagnostic Criteria

n   Lab Studies

n   Stool Analysis

  +Reducing substances

  +Acidic stool (pH lower than 5.5)

n   Urinalysis

  Differential urinary disaccharidases

n   Procedures

n   Sucrose tolerance test

n   CHO hydrogen breath test

  Fermented CHO load in large intestine releases hydrogen that is absorbed into blood and released by lungs

n   Small bowel biopsy

  Measures intestinal disaccharidases

  Final, most definitive test

A Mysterious Diagnosis

n   Correct diagnosis of CSID often long and difficult

n   Symptoms similar in other diseases


  Cow’s milk or soy protein allergy

  Cystic fibrosis

  Celiac disease

n   Patients diagnosed as adults recount h/o feeding difficulties during infancy

Disease Progression

n   Sucrose intolerance usually improves w/ age

n   Symptoms of starch intolerance often disappear within first years of life

n   However, patients do not “grow out” of CSID!

n   While enzyme deficiency remains, pt’s become more tolerant over time

Disease Management

n    Dietary restriction

n    Elimination of sucrose, glucose polymers, starches in 1st year of life

n    After 2-3 years, strict starch restriction can be liberalized as tolerated

n    Pharmacotherapy

n    Sacrosidaise (Sucraid)

   Yeast derived oral form of the sucrase enzyme

   Significantly increases sucrose and starch tolerance

   What is the drug’s efficacy? Research says…

Sacrosidase Therapy For CSID

n      Purpose:

n    To determine if sacrosidase prevented sx’s of diarrhea, abd cramps, gas, bloating in pt’s with CSID


n      Methods:

n    28 subjects (5mo-11yo)

n    Randomized, double-blind trial

   Phase 1: 3 sucrose breath H2 tests

   3 single-dose treatments (placebo, sacrosidase, sacrosidase + milk)

   Phase 2: Dose-response phase

   4 multidose treatments
    10 days FS sacrosidase (1:10; 1:100; 1:1000)

n   Data collected (Phase 2)

  # stools/d, severity of symptoms (for each concentration of enzyme administered + normal diet)

  Baseline period symptoms (sans enzyme therapy + sucrose/starch-free diet)

n   Data Analysis

  ANOVA model

  Non-parameter Wilcoxin signed-rank test

Sacrosidase Therapy For CSID

n   Results

n   Phase 1:

  Breath H2 excretion decreased significantly with sacrosidase, sacrosidase + milk (compared to placebo)

n   Phase 2:

  Significant treatment differences  between higher concentrations vs. lower concentrations

   Higher concentations -> fewer symptoms

n   Conclusion

n   “Sacrosidase is a safe, effective, well-accepted treatment to prevent GI symptoms in patients with CSID consuming a normal diet”

How Does This Apply?    

n   Sacrosidase

n   The active ingredient in Sucraid®

n   Sucraid®

n   Approved by FDA – 1998

n   Oral solution used as a replacement for pt’s w/o enzymes needed to properly break down and absorb sucrose and isomaltose

Milk Allergy: A Brief

n   “The immune system's response to one or more of the proteins found in cow's milk”

n   2-3% of infants are allergic to milk but most tend to outgrow it within the first few years

n   60% milk allergic children outgrow it by the age of four

n   80% outgrow it by the age of 6

Goats’ Milk: What’s the deal?

n     Trace amounts of casein

n     Slightly less lactose than cows milk

n     More easily digestible than cow’s milk

n    Higher amounts of short chain fatty acids

n     If allergic to cows’ milk…

What About A Milk Allergy?

n    Sometimes a milk allergic person can use goat’s milk or soy milk

n    Both milks can be allergenic

n    Many people allergic to cow’s milk are also allergic to goat’s milk


n      Indications – Congenital Sucrase-Isomaltase Deficiency. Orphan Europe, 2002

n      Davis, M.B., et al. Mapping of the gene encoding human sucrase-isomaltase (SI) to chromosome 3q25-26. Cytogenet. Cell Genet. 46:604, 1987.

n      Disaccharide Intolerance I. OMIM, Johns Hopkins University

n      Ritz V, et al. Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant enzyme in the endoplasmic reticulum. Gastroenterology. 125(6):1678-85, 2003.

n      Psychogenic polydipsia with hyponatremia: report of eleven cases. Am J Kidney Dis. 1987 May;9(5):410-6.   

n      Arch Intern Med. 1995 May 8:155(9):953-7.

n      Hum Psychopharmacol. 2002 Jul; 17(5):253-5

n      National Organization for Rare Disorders.

n      Belmont, et al. Congenital Sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis. BMC Pediatrics. 2:1471-2431, 2002.

n      Treem, et al. Sacrosidase therapy for congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 28 (2): 137-142, 1999


Copyright © 2007 , , All Rights Reserved.