Congenital sucrase-isomaltase deficiency (CSID) is a genetic disorder that occurs when the body cannot produce the sucrase-isomaltase enzyme necessary for the proper metabolism of the sugar in fruits (sucrose) and the sugar in grains (maltose). Mutations in the sucrase-isomaltase (SI) gene disrupt production of this enzyme.

We eat carbohydrates in simple and complex molecular formats: monosaccharides, disaccharides, oligosaccharides, and polysaccharides. However, the body can only absorb carbohydrates as simple, single-molecule sugars (monosaccharides).1 Sucrose and maltose are disaccharides; this means two simple sugar molecules combined to form each. Glucose and fructose combine to form sucrose, while two glucose molecules form maltose. Without the necessary sucrase-isomaltase enzyme, individuals with CSID cannot break down sucrose and maltose into absorbable simple sugar forms.

 

Symptoms and Diagnosis

Symptoms can include abdominal pain, bloating, excess flatulence, and diarrhea, and can vary among individuals and depend on the amount of sucrose or maltose consumed. Usually the deficiency becomes apparent as an infant completes weaning and begins consuming fruits, juices, and grains.2 The infant’s inability to break down and absorb sucrose and maltose can lead to difficulties in gaining weight (failure to thrive) and malnutrition.

Research suggests that CSID occurs in 5% of the native populations of Greenland, Alaska, and Canada, but in only 0.02% of North Americans of European descent.1 The variability in symptoms that individuals experience could mean that the incidence is higher. In some cases, deficiency symptoms might resemble those of other gastrointestinal conditions such as irritable bowel syndrome. This can make it a challenging condition to diagnose.

Typically, doctors analyse the sucrase and isomaltase enzyme activity in small bowel tissue biopsies to diagnose the deficiency, which is the gold standard diagnostic method for accuracy and reliability. However, in 2015, researchers challenged this by isolating the specific gene mutation responsible for CSID in the Inuit population. Now there is potential to use blood tests as a method of diagnosis.3

 

When rare is not uncommon: The case of Canada’s Inuit

While scientists already estimated CSID prevalence in the Inuit to be between 5-10%, they had not yet identified the specific genetic cause. One research project started when an Inuit baby girl from Baffin Island experienced severe diarrhea and abdominal distension in hospital after consuming formula containing sucrose. By analyzing her blood, the researchers discovered a mutation in the SI gene c.273_274delAG, which resulted in the loss of SI enzyme expression.3 Cross-referencing this discovery by genotyping a further 128 Inuit individuals from across Nunavut, they found that the gene mutation also occurred in 17% of the sample population.

This is a recessive disorder, in that a person with two copies of the mutated gene (one inherited from each parent) will have the deficiency. Carriers only have one copy of the mutated gene in each cell. Researchers found that 28.5% of the Inuit population in Canada are carriers of the mutated SI gene. Although their statistical analysis of the sample evidence did not change the expected prevalence rate of the congenital deficiency within the Inuit population, the evidence strongly suggests that the gene mutation they identified is responsible for CSID when it occurs in Inuit Canadians.3

For the Inuit, this condition is an example of a gene-environment interaction. The SI gene mutation likely first occurred far back in the ancestry of the Inuit, but it did not result in symptoms until the 1960s when processed and sugary foods entered into their traditionally low-carbohydrate diet. As a result of this study, a simple blood test instead of an intestinal biopsy might be all that is necessary to diagnose this condition in the Inuit, which would allow doctors and patients to begin treatment sooner.

 

Management

Even though CSID is a rare genetic condition, it affects the lives of those who have it in serious ways. Until doctors correctly diagnosed her, the baby girl from Baffin Island not only experienced severe diarrhea and abdominal distension, but also failed to absorb energy and nutrients despite intense high caloric feeding in the hospital. Proper management of this condition requires collaboration with a physician and registered dietitian who can help to control symptoms while ensuring adequate nutrition.

For the most part, management consists of diligently sticking to a sucrose and starch-restricted (or even free) diet. Sometimes, children are better able to tolerate starch after three to four years of age, and rice and corn might be easier to digest. The success rate of restricted diet is mixed. One pediatric study from 2012 found that only 10% of patients on a sucrose and starch-restricted diet avoided CSID symptoms entirely; 60-75% still experienced diarrhea and abdominal pain while 20% had nausea.4 However, this study noted that only about half of the children complied with the prescribed diet.

If dietary restrictions are not enough to control symptoms, a doctor might prescribe sacrosidase (Sucraid®), an enzyme replacement therapy. Sucraid® is in powder form, which is tasteless when mixed with water or other beverages. It is effective in reducing symptoms while easing the burden of maintaining a restrictive diet. In one study examining children with the deficiency, breath tests after ingestion of sucrose showed an increase in breath hydrogen as well as adverse gastrointestinal symptoms. When also consuming sacrosidase, however, breath hydrogen did not rise and symptoms did not present.4

 

Outlook

Modern medicine knows of at least ten mutations in the SI gene that can potentially result in congenital sucrase-isomaltase deficiency.5 However, studies on patients continue to discover new SI gene mutations not documented previously. These findings reinforce the fact that this genetic condition remains a challenge to diagnose. While some researchers were able to find the specific causal mutation for CSID in Canada’s Inuit, current research has yet to do this for other ethnic groups. Nonetheless, after successful diagnosis, dietary restrictions and enzyme replacement therapy (i.e., Sucraid®) offer viable and effective management options. Open communication with one’s health team is important for an improved outcome.


First published in the Inside Tract® newsletter issue 199 – 2016
Photo: diapicard | pixabay.com
1. Buford L et al. Frequency of Sucrase Deficiency in Mucosal Biopsies. JPGN. 2012;55: S28-S30.
2. Congenital sucrase-isomaltase deficiency. US National Library of Medicine: Genetics Home Reference. Available at: https://ghr.nlm.nih.gov/condition/congenital-sucrase-isomaltase-deficiency#genes. Accessed 2016-08-04.
3. Marcadier et al. Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation. CMAJ. 2015;187(2):102-107.
4. Treem WR. Clinical aspects and treatment of congenital sucrase-isomaltase deficiency. JPGN. 2012;55(2):S7-S13.
5. Sucrase-Isomaltase. US National Library of Medicine: Genetics Home Reference. Available at: https://ghr.nlm.nih.gov/gene/SI#conditions. Accessed 2016-07-22.