Most CSID patients begin their diagnosis journey at their pediatrician or primary care physician (PCP). PCPs may diagnose patients with more common causes of diarrhea such as toddler’s diarrhea, irritable bowel syndrome, parasites, or intestinal infections. When treatment for these more common conditions does not alleviate symptoms, a primary care physician will refer the patient to a gastroenterologist, a doctor who specializes in digestive dysfunction.
After referral to a gastroenterologist, the physician will perform a routine analysis of patient well-being, physical examination, clinical history, family history, and diet history. Based on this information, the physician may order tests to determine the exact diagnosis. Often with rare diseases, there is a process of discovery that sometimes requires a systematic process of elimination of other more common ailments. If CSID is suspected, the diagnostic workup could include an upper gastrointestinal endoscopy in which several biopsies (tissue specimens) will be obtained from the duodenum, the first part of the small intestine, and sent for a specialized laboratory analysis of enzymatic activity. This laboratory analysis is commonly known as a disaccharidase assay test using a small bowel biopsy. Measuring intestinal disaccharidases (lactase, sucrase, isomaltase or palatinase, and maltase) through small bowel biopsy is considered the gold standard for diagnosing CSID or Genetic Sucrase-Isomaltase Deficiency (GSID).
Depending on the age of the patient, a treating physician may order a sucrose hydrogen breath test. The hydrogen breath test is a test that can aid in the diagnosis of sucrase deficiency. It uses the measurement of hydrogen in the breath to diagnose gastrointestinal disorders. In the human gut, only a specific type of bacteria in the large intestine is capable of producing hydrogen. The bacteria produce hydrogen when they are exposed to unabsorbed food, particularly sugars and carbohydrates. Large amounts of hydrogen may be produced when there is a problem with the digestion or absorption of food in the small intestine, allowing more unabsorbed food to reach the large intestine. An increase in breath hydrogen output suggests that small intestinal enzymes are not working properly. The hydrogen breath test is not always accurate in identifying CSID since other gastrointestinal conditions can also produce a positive hydrogen breath test. It is also likely to produce gastrointestinal symptoms as a significant amount of sugar is consumed in preparation for this test.
As of 2017, a 13C-sucrose breath test has been proposed to accurately diagnose CSID, but it is not easily obtained. Although this test is considered investigational, it holds great promise for someday being a diagnostic tool.
A stool pH test can sometimes be conducted, but the results are not specific for sucrose malabsorption. If a physician orders a stool pH test in the process of diagnosing CSID, he/she would be looking for a lower-than-normal pH level.
In 2012, genetic testing became commercially available for CSID/genetic sucrase deficiency. While this test cannot be used alone to diagnose CSID, the genetic testing can determine if a person suspected of CSID has any of the mutations on chromosome 3 known to cause CSID. For patients suspected of having CSID, genetic testing offers another test that can help a doctor in diagnosing whether a patient has CSID. For further information, physicians interested in genetic testing should contact the University of Washington Molecular Development Laboratory. Alternately, physicians may order a genetic test kit for patients suspected of CSID/genetic sucrase deficiency by visiting https://www.sucraid.net/hcp/request-an-si-genetic-kit. Studies are in progress to determine whether genetic testing can also be done on intestinal cells, opening the possibility of determining disaccharidase enzyme levels and testing for known genetic mutations for CSID on the same lab sample.
When there is difficulty in diagnosing Genetic Sucrase-Isomaltase Deficiency or the diagnosis is in doubt, a short therapeutic trial with Sucraid® (sacrosidase) Oral Solution may be warranted to assess the response in a patient who is suspected of having sucrase deficiency. Sucraid® has been approved as a diagnostic tool for sucrase deficiency as written in the Sucraid® package insert.
|Test Method||Info Regarding Test Method|
|Small Bowel Biopsy with Disaccharidase Enzyme Testing||• Gold standard for diagnosing sucrase deficiency
• Requires an invasive procedure called an upper endoscopy or EGD
• Sample requires rapid freezing and transfer to a specialized laboratory
|Sucraid® Therapeutic Trial||• Sucrase enzyme replacement therapy
• A 2-week sample of a medication called Sucraid®, which is an exogenous enzyme
|Sucrose Intolerance Hydrogen Breath Test||• Noninvasive procedure
• Requires a special diet 24 hours before test and 12 hours of fasting
• Must catch breath into 6 tubes over a 3-hour time period after ingesting a sucrose solution
• Patients with sucrase deficiency may experience symptoms due to the large consumption of sucrose
|13C Sucrose Breath Test||• Noninvasive
• Newer procedure
• Requires fasting for at least 3 hours
• Must fill breath bags over a 3-hour time period after ingestion of sucrose and glucose
• Mass spectrometry
• Specific test for Genetic Sucrase-Isomaltase Deficiency
• Does not produce symptoms in Genetic Sucrase-Isomaltase Deficiency patients because it does not require excessive consumption of sucrose
|Stool pH Test||• An indirect test for carbohydrate malabsorption
• Not specific for sucrose malabsorption
|SI Genetic Test||• When sucrase activity is <25 μM/min/g
• If disaccharidase assay results are not available for patients with long-term chronic diarrhea and/or abdominal pain, and other common GI disorders have been excluded
• A positive genetic test supports the diagnosis of GSID. The test evaluates for the presence of 37 known pathogenic variants
• A negative test result demonstrates the absence of one or more of these variants. However, other unidentified pathogenic variants may exist, so a negative test is not conclusive for absence of the disease
|4-4-4 Oral Sugar Challenge||• 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. Mix until sugar is completely dissolved
• Step 2: Drink it on an empty stomach
• Step 3: See if symptoms such as bloating, gas and diarrhea occur during the next 4-8 hours; this suggests sucrose intolerance is possible