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Sucrase-isomaltase

Sucrase-isomaltase (SI) is a glucosidase enzyme located on the brush border of the small intestine. 

The highest prevalence rates are seen in the Inuit populations of Greenland (5–10%), Alaska (3–7%) and Canada (about 3%). 

European descent prevalence ranges from 0.2% to 0.05%. 

There is a lower prevalence reported in African Americans and Hispanics compared to Caucasians.

It is a dual-function enzyme with two domains, one serving as the isomaltase, the other as a sucrose alpha-glucosidase.

It is expressed  in the apical membranes of enterocytes.

It digest dietary carbohydrates such as starch, sucrose and isomaltose. 

By processing of broken-down products, energy in the form of ATP can be generated.

Gene location  is chromosome 3.

Sucrase-isomaltase consists of two enzymatic subunits: sucrase and isomaltase. 

Sucrase-isomaltase enzyme is anchored in the intestinal brush border membrane by a hydrophobic segment located near the N-terminal of the isomaltase subunit.

Glycosylation is necessary to target the protein to the apical membrane.

The O-linked glycosylation is necessary to target the protein to the apical membrane.

Sucrase-isomaltase is composed of duplicated catalytic domains, N- and C-terminal. 

The sucrase-isomaltase exists as a monomer. 

A deficiency of the enzyme is responsible for sucrose intolerance. 

Congenital sucrase-isomaltase deficiency (CSID), called genetic sucrase-isomaltase deficiency (GSID), and sucrose intolerance.

CSID is a genetic, intestinal disorder that is caused by a reduction or absence of sucrase and isomaltase.

A relationship between mutations in sucrase-isomaltase and chronic lymphocytic leukemia (CLL) has been identified, causing a loss of enzyme function by blocking the biosynthesis of SI at the cell surface.

In sucrose intolerance or genetic sucrase-isomaltase deficiency (GSID) is the condition in which sucrase-isomaltase, an enzyme needed for proper metabolism of sucrose and starch, is not produced or the enzyme produced is either partially functional or non-functional in the small intestine. 

All sucrase-isomaltase deficiency (GSID) patients lack fully functional sucrase, while the isomaltase activity can vary from minimal functionality to almost normal activity. 

Therefore some GSID patients are better able to tolerate starch in their diet than others with GSID.

Associated symptoms: abdominal cramps and bloating, diarrhea and constipation, vomiting, hypoglycemia, headaches, poor weight gain and growth

Sucrose intolerance can be caused by genetic mutations in which both parents must contain this gene for the child to carry the disease.

Sucrose intolerance can also be caused by irritable bowel syndrome, aging, or small intestine disease.

Tests used to help determine if a person has sucrose intolerance is done by biopsying the small intestine. 

Other tests can aid in the diagnosis of GSID are the sucrose breath test, and a genetic test which tests for the absence of certain genes which are thought to be responsible for GSID.

Sucrose  which is also called saccharose, is a disaccharide and is a two-sugar chain composed of glucose and fructose which are bonded together. 

It is referred to as table beet, or cane sugar. 

It was previously believed that most cases of sucrose intolerance were due to an autosomal recessive, genetic, metabolic disease, but patients with heterozygous and compound heterozygous genotypes can have symptom presentation as well. 

When disaccharides are consumed, they must be broken down into monosaccharides by enzymes in the intestines before they can be absorbed. 

Monosaccharides, or single sugar units, are absorbed directly into the blood.

A deficiency of sucrase may result in malabsorption of sugar.

Since sucrase-isomaltase is involved in the digestion of starches, some GSID patients may not be able to absorb starches as well. 

With sucrose intolerance it os important to minimize sucrose consumption as much as possible. 

Chronic gastrointestinal symptoms that are fairly common but difficult to diagnose may be caused by congenital sucrase-isomaltase deficiency (CSID). 

CSID is an inherited condition characterized by a dysfunctional digestive enzyme.

Sucrase-isomaltase, breaks down the compound sugars sucrose, table sugar, and starch sugars so they will be small enough to be absorbed from the gastrointestinal tract.

In addition, a primary gastrointestinal disorder such as a gastrointestinal infection, celiac disease or Crohn’s disease, can transiently suppress the digestive function of sucrase-isomaltase.

This causes an acquired form of sucrase-isomaltase deficiency (SID). 

The sucrase-isomaltase enzyme is responsible for the digestion of all foods containing sucrose and approximately 60% to 80% of all foods containing starch sugars.

With sucrose-isomaltase deficiency, sucrose or starch sugars are not absorbed from the gastrointestinal tract, and they draws excess water by osmosis, creating watery diarrhea.

The unabsorbed  food is broken down by the normal bacteria that reside in the colon by a process called fermentation.

The byproducts of fermentation include the production of excess gas and an acidic environment.

Distinctively, congenital sucrase-isomaltase deficiency symptoms are frequent and daily occurrences.

CSID symptoms are lifelong.

CSID symptoms occur after eating.

Symptoms of SID can range from mild to severe.

Symptoms of SID include chronic, watery, acidic diarrhea; intestinal gas and bloating; nausea; and abdominal pain.

In infants and toddlers watery diarrhea and failure to thrive are the most common symptoms: Other symptoms include abdominal distention, gassiness, colic, irritability, excoriated buttocks, severe diaper rash due to acidic diarrhea, indigestion, and vomiting.

Adults with CSID are usually lean, with a low body-mass index and an aversion to eating carbohydrates and “sweets.” 

Because CSID is an inherited condition, patients with CSID often have close relatives who also experience chronic diarrhea.

To diagnose CSID, measures the level of activity of four intestinal enzymes that digest compound sugars, also called disaccharides must be done.

The four disaccharides digested in the small intestine are lactose, sucrose, maltose, and isomaltose.

This diagnostic test a disaccharidase assay, is conducted on tissue samples taken from the small intestine.

If the level of sucrase activity is below the level considered necessary for normal sucrase function, the patient will be diagnosed with CSID.

Breath tests are useful screening tools but are not specific enough for a confirmed diagnosis of CSID.

The hydrogen/methane breath test:the amount of hydrogen and methane gases a person exhales after consuming sugary water. 

The exhaled breath is collected at 30-minute intervals over a three-hour period after drinking the sugary water. 

With CSID and there are little or no working sucrase-isomaltase enzymes in the intestines and greater than normal levels of hydrogen and/or methane are generated and exhaled in the breath. 

The carbon-13 (13C) breath test uses a stable isotope of carbon that occurs naturally in sucrose, making it possible to track a person’s ability to digest and absorb sucrose by measuring the amount of 13CO2 exhaled after drinking a sugar-water solution. 

If the cumulative amount of 13CO2 exhaled is below the normal level that occurs when sucrose is digested by sucrase, the person may have CSID.

The 13C-breath test is more definitive for CSID than the hydrogen/methane breath test although neither test is validated to provide, by themselves, a diagnosis for CSID.

A genetic test for the gene SI, which codes for the enzyme sucrase-isomaltaseis available.

A positive genetic test for one or more of the 37 SI gene variations known to cause CSID.

There are more than 2,000 different variations of the SI gene, and many of these variations have not yet been investigated for their ability to cause CSID.

If a two-week therapeutic trial with an enzyme replacement shows a reduction of symptoms it is considered diagnostic for CSID.

Management:

Diet modification that eliminates or restricts the consumption of foods containing sucrose or starch sugars.

The use of enzyme replacement therapy to replace the action of the sucrase enzyme that is deficient. 

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