Diagnosis

How is Congenital Sucrase-Isomaltase Deficiency Diagnosed?

It is easy to misdiagnose Congenital Sucrase-Isomaltase Deficiency (CSID), especially if the patient presents with nonspecific symptoms. A correct diagnosis of CSID may be delayed while other, more common causes of severe chronic diarrhea are considered.1

Infants with CSID are often misdiagnosed with food allergies or intolerance to cow’s milk or soy protein. An improvement in symptoms while ingesting a casein-hydrosylate formula may be interpreted as further proof for this mistaken diagnosis when the response actually reflects the switch from dietary carbohydrates to dietary glucose polymers, which are not dependent on sucrase-isomaltase activity for digestion.1

Once the patient outgrows infancy and a larger variety of foods is added to the diet, it becomes increasingly more difficult to correctly identify sucrose as the explicit cause of gastrointestinal (GI) symptoms. In addition, there may be a high incidence of comorbidity between CSID and other enzyme deficiencies involved in carbohydrate digestion.

Such comorbidities and/or misdiagnoses may include allergic gastroenteropathy, cystic fibrosis, celiac disease, severe viral gastroenteritis, lactose intolerance, glucose-galactose intolerance, or other causes of intractable diarrhea. The presence of mild steatorrhea is commonly used to support these alternate diagnoses.1

As the table below indicates, there are several tests that may help in the diagnosis of CSID.

Table 1.

Diagnostic Tools to Assess Sucrase Enzyme Activity

Test Method

Disaccharidase (including sucrase) assay via small bowel biopsy2

Background Information
  • The historically definitive assay for diagnosing CSID
  • Tissue sample is obtained from the distal duodenum or proximal jejunum at the time of endoscopy
  • Assay is only performed by a few specialized laboratories
  • For more information on how to establish disaccharidase assay testing, call 1-800-705-1962
Description and Interpretation
  • Tissue biopsies obtained during gastroendoscopy sent to a specialized lab for analysis of disaccharidase activity
  • Sucrase activity is considered abnormal when it is below the 10th percentile (<25 U)2
  • However, a sucrase deficiency diagnosis should also be considered when sucrase activity is below the 20th percentile (<33 U) and is assessed in combination with gastrointestinal signs and symptoms2
Pros and Cons

Pros:

  1. Historically definitive assay for assessing sucrase activity
  2. Well-established normal values
  3. Explicit measure of endogenous activity
  4. Sucrase and lactase results available for free

Cons:

  1. Invasive, requires esophago-gastroduodenoscopy (EGD)
  2. Cold-chain sample handling required
  3. Not available at most general reference labs; assay is only performed by a few specialized laboratories
  4. This test will not distinguish between CSID and acquired (secondary) sucrase deficiency
Test Method

Carbon-13 sucrose breath test (13C SBT)

Background Information
  • A noninvasive test that is short in duration and can be administered by the patient at home
  • A healthcare professional can order the test by calling 1-800-705-1962
  • To perform the test, patients follow the simple instructions included in each kit and ship the test kit back via a prepaid shipping label
  • Test results will be provided to the physician’s office within 24 hours of receiving the test kit
  • Patients with sucrase deficiency may experience symptoms caused by the large consumption of sucrose associated with the test
Description and Interpretation
  • Sucrase is considered abnormal when, after consuming a 20-g sucrose solution, a cumulative [13C] CO2 exhalation over 90 minutes is below the 10th percentile, which is ≤3.9% for men and 5.2% for women3
Pros and Cons

Pros:

  1. Easy and simple, at-home test
  2. 13C test duration is 90 minutes rather than 180 minutes for a hydrogen-methane test
  3. Sensitivity and specificity of small sample size is high relative to sucrase assays4
  4. Does not rely on secondary fermentation
  5. Discontinuation of antibiotics not required3

Cons:

  1. Only available from one laboratory
  2. Does not clarify etiology
  3. At-home test, which may be impacted by adherence to test procedures
  4. This test will not distinguish between CSID and acquired (secondary) sucrase deficiency
Test Method

Sucrose hydrogen-methane breath test

Background Information
  • A noninvasive test that is short in duration and can be administered by the patient at home
  • A healthcare professional can order the test by calling 1-800-705-1962
  • To perform the test, patients follow the simple instructions included in each kit and ship the test kit back via a prepaid shipping label
  • Test results will be provided to the physician’s office within 24 hours of receiving the test kit
  • Patients with sucrase deficiency may experience symptoms caused by the large consumption of sucrose associated with the test
Description and Interpretation
  • Positive when the sequential net increase over 3 hours in exhaled hydrogen is >20 ppm, methane is >12 ppm, or both are >15 ppm over a previous baseline level (the first breath sample or any earlier time sample)5
  • Sucrase deficient patients will likely have symptoms during or shortly after the test because of the 50-g sucrose load
Pros and Cons

Pros:

  1. Easy and simple, at-home test
  2. Well-established use6
  3. Effective when assessed with gastrointestinal symptoms during and after the test7

Cons:

  1. May be impacted by bacterial overgrowth in the small intestine (SIBO)
  2. Patients may not produce hydrogen or methane, or may have a high baseline of either resulting in false negatives
  3. Does not clarify etiology
  4. Potential for false positives (low specificity)
  5. Potential for false negatives (low sensitivity)
  6. At-home test, which may be impacted by adherence to test procedures
  7. This test will not distinguish between CSID and acquired (secondary) sucrase deficiency
Test Method

The 4-4-4 oral sucrose challenge test

Background Information
  • The test is short, simple and can be performed in the privacy of the patient’s home
  • Step 1: Stir 4 tablespoons of ordinary table sugar into a 4-ounce glass of water and mix until sugar is completely dissolved
  • Step 2: Drink it on an empty stomach
  • Step 3: If symptoms such as bloating, gas, and diarrhea occur during the next 4 to 8 hours, this suggests possible sucrose intolerance
Description and Interpretation
  • After consuming a 50-g sucrose load, sucrase deficient patients will have unabsorbed sucrose available for colonic fermentation and resulting symptoms such as gas, bloating, distention, and diarrhea.
  • A positive test results in moderate to severe gastrointestinal symptoms occurring within about 4 hours after drinking a sucrose solution
Pros and Cons

Pros:

  1. Very easy and simple, at-home test
  2. Inexpensive
  3. Patients who are sucrase deficient will have clear symptoms when consuming a 50-g sucrose load after fasting

Cons:

  1. Subject to symptom interpretation by patients and adherence to test procedure
  2. Unknown sensitivity and specificity
  3. Not appropriate for infants, young children, and geriatric patients, and those with co-morbid conditions. Patients may have severe symptoms if they are very sensitive to sugar
Test Method

Therapeutic trial of sacrosidase enzyme replacement

Background Information
  • If clinically inappropriate or difficult to perform a biopsy or if a diagnosis is in doubt, a short two-week trial period with enzyme replacement therapy may be warranted
  • Sucraid is the only FDA-approved enzyme replacement therapy indicated for the treatment of genetically determined sucrase deficiency, which is part of CSID8
Description and Interpretation
  • Sucrase deficient subjects should respond very positively, with significant symptom resolution
Pros and Cons

Pros:

  1. Simple and available
  2. Therapeutic response can be dramatic

Cons:

  1. Potential placebo response
  2. Requires a free-trial prescription
  3. Subject to variable symptom interpretation and adherence to treatment procedures

Learn How to Order Sucraid from Our Specialty Pharmacy

Important Safety Information for Sucraid® (sacrosidase) Oral Solution

  • Sucraid may cause a serious allergic reaction. Patients should stop taking Sucraid and get emergency help immediately if any of the following side effects occur: difficulty breathing, wheezing, or swelling of the face. Care should be taken when administering initial doses of Sucraid to observe any signs of acute hypersensitivity reaction.
  • Do not use Sucraid (sacrosidase) Oral Solution with patients known to be hypersensitive to yeast, yeast products, papain, or glycerin (glycerol).
  • Although Sucraid provides replacement therapy for the deficient sucrase, it does not provide specific replacement therapy for the deficient isomaltase.
  • Adverse reactions as a result of taking Sucraid may include worse abdominal pain, vomiting, nausea, diarrhea, constipation, difficulty sleeping, headache, nervousness, and dehydration.
  • Before prescribing Sucraid to diabetic patients, the physician should consider that Sucraid will enable sucrose hydrolysis and the absorption of those hydrolysis products, glucose and fructose.
  • The effects of Sucraid have not been evaluated in patients with secondary (acquired) disaccharidase deficiency.
  • DO NOT HEAT SOLUTIONS CONTAINING SUCRAID. Do not put Sucraid in warm or hot fluids. Do not reconstitute or consume Sucraid with fruit juice since the acidity of the juice may reduce the enzyme activity of Sucraid. Half of the reconstituted Sucraid should be taken at the beginning of the meal or snack and the other half during the meal or snack.
  • Sucraid should be refrigerated at 36°F-46°F (2°C-8°C) and should be protected from heat and light.

Indication

Sucraid®(sacrosidase) Oral Solution is an enzyme replacement therapy for the treatment of genetically determined sucrase deficiency, which is part of Congenital Sucrase-Isomaltase Deficiency (CSID).