For Physicians

Overview of CSID

Congenital Sucrase-Isomaltase Deficiency (CSID) is an autosomal recessive disease of the small intestine characterized by a failure to absorb sucrose, and was first discovered in 1960 by Weijers and colleagues. The disease was originally defined by undetectable sucrase activity, a decrease of maltase activity to nearly one third of the normal level, and a varying degree of isomaltase activity. All CSID patients lack functional sucrase activity, but the degree of isomaltase activity varies, suggesting that the disease is not a consequence of a complete lack of SI gene expression. Therefore, CSID is considered a heterogeneous condition.

Failure to absorb dietary sucrose and starch may impact the absorption of other nutrients and the hormonal regulation of gastrointestinal function. Unabsorbed carbohydrates inhibit gastric emptying and accelerate small-intestinal transit and contribute to malabsorption of starch, fat, and monosaccharides. Normal postprandial increases in hormones such as insulin, C-peptide, and gastric inhibitory peptide may be disrupted. For these reasons, patients with CSID are at risk for chronic malnutrition; indeed, failure to thrive is one of the characteristics of the disease state. In addition to diarrhea, fermentation of excess dietary disaccharides by resident gut bacteria can result in gassiness, abdominal distention, and pain.

Clinical Presentation

The clinical presentation of CSID can range from mild to severe.8 Infants do not manifest symptoms of CSID until they begin to ingest sucrose- and starch-containing foods (e.g., juices, solid foods, medications sweetened with sucrose). Chronic, watery diarrhea and failure to thrive are the most common symptoms in infants and toddlers; other consequences include abdominal distention, gassiness, colic, irritability, excoriated buttocks, diaper rash, and vomiting. In some societies, notably Greenland Eskimos and some Alaskan Natives, a low-carbohydrate, high-protein, high-fat diet may mask symptoms. A small number of patients may require hospitalization for diarrhea and dehydration, malnutrition, muscle wasting, and weakness.9

In adults, symptoms persist, but may appear to be less severe than those experienced by children. CSID is not, however, a disease that a patient can "outgrow." Normal sucrase-isomaltase enzyme activity is not stimulated through repeated or cumulative sucrose/isomaltose challenges. In some adults, symptoms may be limited to an increase in bowel frequency, abdominal distention, and flatulence, although episodic watery diarrhea upon ingestion of high levels of sucrose may occur.3 In some patients, diarrhea may alternate with constipation, leading to a misdiagnosis of irritable bowel syndrome.

As with pediatric patients, the clinical presentation in adults is variable. With the introduction of dietary sucrose, some patients may experience several severe effects from this disease, while others may experience only mild symptoms.

Common Misdiagnoses

The diagnosis of CSID can be missed, especially if patients have mild, nonspecific symptoms. In most cases of CSID, correct diagnosis is delayed while other causes of severe chronic diarrhea are entertained.10

Commonly, patients are diagnosed with allergy or intolerance to cow's milk or soy protein. An improvement in symptoms while ingesting a casein-hydrosylate formula may be interpreted as support for this mistaken diagnosis, when it in fact reflects the switch from carbohydrate to glucose polymers, which are dependent on glucoamylase activity for digestion.3 Once infancy is past and a larger variety of foods are added to the diet, it is increasingly difficult to correctly identify sucrose as the cause of symptoms.

Allergic gastroenteropathy, cystic fibrosis, celiac disease, severe viral gastroenteritis, lactose intolerance, glucose-galactose intolerance or other causes of intractable diarrhea are often considered in diagnosis. Mild steatorrhea is commonly used to support these diagnoses.11

Diagnostic Workup

CSID can be diagnosed definitively by correlating intestinal biopsy tissue samples that have normal morphology interpretation with the abnormal results from disaccharide analyses (>2 standard deviations below normal values). Therefore, it is recommended that clinicians collect two additional specimens when conducting upper endoscopy with biopsy among high-risk patient groups. One biopsy tissue sample is intended for morphology interpretation, while the other sample is intended for disaccharide tissue testing. All four enzymes should be ordered (lactase, sucrase, maltase, and palatinase) to inform whether the cause of gastrointestinal symptoms is some form of carbohydrate malabsorption.

Method Positive Result
Stool pH pH < 6.0
Sacrosidase Therapeutic Trial Marked decrease in symptoms (diarrhea, gas, bloating, cramps) within one week
Sucrose Breath Test >10 ppm H2 over baseline
Small Bowel Biopsy
Disaccharidase Measurements		 ≥2 SD below mean for sucrase activity ± isomaltase activity with normal lactase activity and normal villous architecture

Table 1. Positive Diagnosis of CSID1, 2

Sucrose breath hydrogen tests have been extensively validated in children with CSID and normal controls.17 The test is based upon the fact that in CSID, unabsorbed sucrose is converted in the colon to methane, carbon dioxide, and hydrogen gases by bacteria. Hydrogen gas is absorbed into the bloodstream and eliminated via expired air. Thus, following a loading dose of sucrose, the amount of hydrogen in expired air is proportional to its intraluminal production.17 Among sucrose-tolerant subjects, administration of a 1.0 to 2.0 g/kg oral sucrose load is associated with a change in breath hydrogen of <10 parts per million. Among patients with CSID, the same load is associated with an elevation in breath hydrogen exceeding 20 parts per million between 90 and 180 minutes after ingestion of sucrose.3 However, it must be noted that some patients are so-called “non-hydrogen producers.” The prevalence of non-hydrogen producers has been estimated at between 2% to 20%.18-20 These data suggest that the breath hydrogen test is an unreliable diagnostic parameter for CSID.

Treatment Options

In patients with CSID and overt symptoms that warrant treatment, two major modalities exist: non-pharmacologic and pharmacologic. Until recently, the treatment of CSID consisted of lifelong adherence to a strict sucrose-free diet. (It is seldom necessary to make this diet starch-free except in infants or in patients in whom a sucrose-free diet does not provide adequate relief of symptoms.) However, given the sucrose content of Western diets, patient compliance with a sucrose-free diet is, at best, difficult. Patient noncompliance is common and often accompanied by continued chronic gastrointestinal symptoms, decreased weight for height, and decreased weight for age.8,9,12

Enzyme replacement therapy with Sucraid® offers a pharmacologic alternative to sucrose-free diets. Sucraid® is an effective, simple-to-administer option for the management of sucrase deficiency that reduces or eliminates the need for dietary restrictions and eliminates the symptoms of CSID in the majority of patients.1

Given its demonstrated efficacy in correcting sucrase deficiency, if a specific CSID diagnosis is in doubt, it may be warranted to conduct a short therapeutic trial (e.g., one week) with Sucraid® (sacrosidase) Oral Solution to assess response in a patient suspected of sucrase deficiency.1 Substantial attenuation or elimination of symptoms while the patient is on a normal, sucrose-containing diet suggests the presence of CSID.

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REFERENCES

  1. Sucraid Prescribing Information. QOL Medical. Kirkland, WA. 2010.
  2. Gray GM. Carbohydrate digestion and absorption. Role of the small intestine. N Engl J Med. 1975;292:1225-1230.
  3. Treem WR. Congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 1995;21:1-14.
  4. Hunziker W, Spiess M, Semenza G, Lodish HF. The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein. Cell. 1986;46:227-234.
  5. Naim HY, Roth J, Sterchi EE, et al. Sucrase-isomaltase deficiency in humans. Different mutations disrupt intracellular transport, processing, and function of an intestinal brush border enzyme. J Clin Invest. 1988;82:667-679.
  6. Peterson ML, Herber R. Intestinal sucrase deficiency. Trans Assoc Am Physicians. 1967;80:275-283.
  7. Welsh JD, Poley JR, Bhatia M, Stevenson DE. Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Gastroenterology. 1978;75:847-855.
  8. Antonowicz I, Lloyd-Still JD, Khaw KT, Shwachman H. Congenital sucrase-isomaltase deficiency. Observations over a period of 6 years. Pediatrics. 1972;49:847-853.
  9. Gudmand-Hoyer E. Sucrose malabsorption in children: a report of thirty-one Greenlanders. J Pediatr Gastroenterol Nutr. 1985;4:873-877.
  10. Ament ME, Perera DR, Esther LJ. Sucrase-isomaltase deficiency - a frequently misdiagnosed disease. J Pediatr 1973;83:721-727
  11. Gudmand-Hoyer E, Krasilnikoff PA, Skovberg H. Sucrose-isomaltose malabsorption. In: Draper H, ed. Advances in nutritional research; vol 6. New York: Plenum Press, 1984:233-269.
  12. Kilby A, Burgess EA, Wigglesworth S, Walker-Smith JA. Sucrase-isomaltase deficiency. A follow-up report. Arch Dis Child. 1978;53:677-679.
  13. Data on file, QOL Medical. Long-term sucrase enzyme therapy for congenital sucrase-isomaltase deficiency (study report). 1998.
  14. Treem WR, McAdams L, Stanford L, Kastoff G, Justinich C, Hyams J. Sacrosidase therapy for congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 1999;28:137-142.
  15. Robayo-Torres CC, Opekun AR, Quezada-Calvillo R, et al. 13C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients. J Pediatr Gastroenterol Nutr. 2009;48:412-418.
  16. Treem WR, Ahsan N, Sullivan B, et al. Evaluation of liquid yeast-derived sucrase enzyme replacement in patients with sucrase-isomaltase deficiency. Gastroenterology. 1993;105:1061-1068.
  17. Perman JA, Barr RG, Watkins JB. Sucrose malabsorption in children: noninvasive diagnosis by interval breath hydrogen determination. J Pediatr. 1978;93:17-22.
  18. Bond JH, Levitt MD. Use of breath hydrogen (H2) in the study of carbohydrate absorption. Am J Dig Dis. 1977;22:379-382.
  19. Douwes AC, Schaap C, van der Klei-van Moorsel JM. Hydrogen breath test in schoolchildren. Arch Dis Child. 1985;60:333-337.
  20. Joseph F, Jr., Rosenberg AJ. Breath hydrogen testing: diseased versus normal patients. J Pediatr Gastroenterol Nutr. 1988;7:787-788.
  21. Treem WR. Clinical heterogeneity in congenital sucrase-isomaltase deficiency. J Pediatr. 1996;128:727-729.

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Important Safety Information

For a complete discussion of indications, usage, contraindications, warnings, precautions, adverse reactions, and overdosage, please see full prescribing information attached. Do not use Sucraid® with patients known to be hypersensitive to yeast, yeast products, or glycerin (glycerol). Sucraid may contain papain which can cause allergic reactions in some patients. Adverse experiences with Sucraid in clinical trials were generally minor and were frequently associated with underlying disease. In clinical studies of up to 54 months duration, physicians treated a total of 52 patients with Sucraid. The adverse experiences and respective number of patients reporting each event were as follows: abdominal pain(4), vomiting(3), nausea(2), diarrhea(2), constipation(2), insomnia(1), headache(1), nervousness(1), and dehydration(1). Note: diarrhea and abdominal pain can be a part of the clinical presentation of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency. The effects of Sucraid have not been evaluated in patients with secondary (acquired) disaccharidase deficiency. In one clinical trial, one patient, a four year old boy who was being treated for asthma, experienced severe wheezing necessitating admission into the ICU. While reported reactions are extremely rare, care should be taken when administering initial doses of Sucraid to observe any signs of acute hypersensitivity reaction. Care should be taken to administer initial doses of Sucraid near a facility where acute hypersensitivity reactions can be adequately treated.1