Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency 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 Genetic Sucrase-Isomaltase Deficiency 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, Genetic Sucrase-Isomaltase Deficiency 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 Genetic Sucrase-Isomaltase Deficiency 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.
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.]4
The clinical presentation of Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency can range from mild to severe chronic, watery diarrhea and/or abdominal pain.5 Infants do not manifest symptoms of Genetic Sucrase-Isomaltase Deficiency 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 ethnic populations, notably Greenland Eskimo and some Alaskan Native, 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.6
Symptoms persist in adults, but may appear less severe than those experienced by children. Genetic Sucrase-Isomaltase Deficiency 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 varies. With the introduction of dietary sucrose, some patients with the disease may experience several severe effects, while others may experience only mild symptoms.