Congenital Sucrase-Isomaltase Deficiency (CSID) Symptoms and Treatment

About CSID

What is Congenital Sucrase-Isomaltase Deficiency?

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.

What is Sucrase-Isomaltase?

Sucrase-isomaltase (SI) is one of four integral glycoproteins expressed in the brush border membrane of the small intestine.³ Sucrase-isomaltase is an enzyme responsible for catalyzing the hydrolysis of dietary sucrose and starch into glucose and fructose for transport into the blood stream. This glycoprotein is comprised of two highly homologous subunits, sucrase and isomaltase. [In the normal intestine, SI is synthesized as a single-chain polypeptide precursor with two active sites, which is cotranslationally modified by N-glycosylation in the endoplasmic reticulum.⁵

How common is CSID?

Congenital sucrase-isomaltase deficiency is a rare, autosomal recessively inherited disease.³ There is wide phenotypic heterogeneity in CSID, with symptoms ranging from absent or minimal to life-threatening. The symptoms are nonspecific and similar to other common gastrointestinal disorders. As such, it is likely that the true prevalence of CSID is underestimated, and that numerous patients suffering from chronic diarrhea and/or abdominal pain as a result of CSID remain undiagnosed (Figure 3).

The prevalence of heterozygotes (e.g., those with a level of sucrase activity below the lower limit for the normal population) was estimated in one study to be 8.9% in the United States population.⁶ Other studies have estimated the prevalence of heterozygotes to be as low as 2% in Caucasian populations.⁷ The prevalence of CSID is significantly higher among persons of Greenland, Alaskan, or Canadian Eskimo descent. For example, the prevalence of sucrose malabsorption among Greenland natives is 10.5%.³

What symptoms should I look for?

The clinical presentation of CSID can range from mild to severe chronic, watery diarrhea and/or abdominal pain.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 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.

What are some common misdiagnoses?

The diagnosis of CSID can be missed, especially if patients have mild, nonspecific symptoms. Correct CSID diagnosis may be delayed while other causes of severe, chronic diarrhea are entertained.¹⁰

Commonly, patients are misdiagnosed with food 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 explicit cause of symptoms. In addition, there may be high co-morbidities between CSID and other enzymatic deficiencies involved in carbohydrate digestion.

Such co-morbidities 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. Mild steatorrhea is commonly used to support these diagnoses.¹¹

How is CSID diagnosed?

The diagnosis of CSID can be missed, especially if patients have mild, nonspecific symptoms. Correct CSID diagnosis may be delayed while other causes of severe, chronic diarrhea are entertained.¹⁰

The various methods for diagnosing CSID are shown in the following table.

Methods to Diagnose CSID

Method	Positive Result	False (+)	False (-)
Stool pH	pH < 6.0	Any carbohydrate malabsoption	Decreased colonic bacteria
Sucrose Breath Test	< 20 ppm H₂ over baseline	Diffuse villous injury	Decreased colonic bacteria, non-H₂ producer
Small Bowel Disaccharidase Measurements	≥ 2 SD below mean for sucrase activity +/- isomaltase activity with normal lactase activity and normal villous architecture	Improper specimen handing. Biopsy too proximal in duodenum.
Sucraid^® Therapeutic Trial	Marked decrease in symptoms (diarrhea, gas, bloating, cramps) within one week	Secondary sucrase deficiency	Inadequate dose and improper administration

Table 1. Methods to diagnose CSID

It may sometimes be clinically inappropriate, difficult or inconvenient to perform a small bowel biopsy or breath hydrogen test to make a diagnosis of CSID. If the diagnosis is in doubt, it may be warranted to conduct a short therapeutic trial (e.g., one week) with Sucraid^® to assess response in a patient suspected of sucrase deficiency.¹ Sucraid^® is indicated for a therapeutic trial.

The effects of Sucraid^® have not been evaluated in patients with secondary (acquired) disaccharidase deficiencies.

What are the 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 However, in a clinical trial testing a restricted diet, 75% of patients were not asymptomatic.

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 both the need for dietary restrictions and the symptoms of CSID in the majority of patients.⁵


Figure 5. 97% of parents rated their childrens' symptoms as "improved significantly".¹³		Figure 6. In long term clinical trials, 81% of Sucraid^® patients became asymptomatic.¹⁴

Given the demonstrated efficacy in correcting sucrase deficiency, 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.

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