Disaccharidase Deficiency - Types, Symptoms, and Diagnosis

Introduction

Disaccharidases are glycoside hydrolase enzymes that break down disaccharides into monosaccharides and are located in the intestinal brush border. The small bowel is overloaded with carbohydrate substrate due to a congenital or acquired impairment of these crucial enzymes, which raises osmotic stress and increases luminal fluid. Additionally, too much fermentable substrate causes the small bowel to produce more gas. Slight intestinal distension from this can cause abdominal pain, especially in people with visceral hypersensitivity, as well as early fullness and bloating in people with functional dyspepsia and irritable bowel syndrome.

What Are the Disaccharidases and Their Functions?

Disaccharidases are a family of tiny intestinal brush border enzymes crucial for breaking disaccharides (sucrose, lactose, maltose, and trehalose) into monosaccharides, which are then absorbed from the gastrointestinal tract. Sucrase plays a vital function in the digestion of starch oligomers into glucose and is responsible for breaking down sucrose into glucose and fructose. Sucrose is a prominent ingredient in the Western diet and is present in many meals, including fresh fruits like peaches and bananas, desserts like cookies and chocolates, and many well-known drinks. The amylase-produced branching poly- and oligosaccharides, which neither amylase nor maltase can digest, are broken by isomaltase into -1,6 links. With amylase, glucose amylase further hydrolyzes oligosaccharides into glucose in the brush boundary. The brush border enzyme sucrase-isomaltase functions in combination with sucrase. The cells lining the small intestine generate maltase, which converts the disaccharide maltose to simple sugar glucose. Foods that have been caramelized and contain starch produce maltose.

What Happens in Disaccharidase Deficiency?

The inability to digest certain everyday meals can be caused by deficiencies in any of these enzymes, which can cause dyspepsia, bloating, and abdominal pain in children, which can resemble the signs of functional gastrointestinal disorders (FGIDs). FGIDs are a broad category of gastrointestinal disorders not brought on by structural or metabolic anomalies. Children of all ages frequently suffer from these ailments. It is thought that a portion of FGID patients has linked disaccharidase deficiencies, which, if discovered, can improve the affected individuals' treatment outcomes. However, disaccharidase deficits can be acquired or congenital, further complicating the proper diagnosis and treatment of these patients. Although once considered uncommon, disaccharidase deficiency is linked to numerous genes. Therefore, genetic testing is used to identify the 26 distinct mutations that make up congenital sucrase-isomaltase deficiency (CSID), also known as genetic sucrase-isomaltase deficiency (GSID), of which four are the most common. Although it is autosomal recessive, the mutation's severity can significantly impact how the disorder manifests.

What Are the Different Types of Disaccharidase Deficiency?

The different types of disaccharidase deficiency are

• Congenital Lactase Deficiency - Genetic differences are the cause of primary lactase deficiency and congenital deficits of disaccharidases. An uncommon condition known as congenital lactase deficiency is inherited via an autosomal recessive mechanism. The lactase gene for humans can be found on chromosomes 2q21–22. The gene for lactase-phlorizin hydrolase is located more than two megabases distant from the locus for congenital lactase deficiency, located 350 kilobases away.

• Primary (Adult-Type) Hypolactasia - The most prevalent kind of lactose insufficiency, is defined by a reduction in lactase activity that begins after the age of three. After weaning, lactase expression decreases because of a downregulation of transcription or destabilization of mRNA transcripts brought on by developmentally controlled DNA-binding proteins.

• The inheritance of an autosomal dominant mutation, which prevents the normal maturational reduction in lactase expression, is thought to cause lactase persistence. The control of enzyme activity has been linked to the single-nucleotide polymorphism (SNP) -13910 T/C upstream of the coding gene. In whites, adult-type hypolactasia is linked to the CC genotype of the SNP -13910 T/C upstream of the lactase gene, whereas lactase persistence is related to the TC and TT genotypes. Near the -13910 position, several other polymorphisms have been found that are linked to lactase persistence in the Middle East and Africa.

• Congenital Sucrase-Isomaltase Deficiency - Affects 10 % of Greenlandic Eskimos and 0.2 % of North Americans of European descent. This condition is autosomal recessive. The sucrase-isomaltase gene is situated at location 3q25–26 on chromosome 3. Intestinal sucrase activity is undetectable in those affected, and isomaltase activity is diminished. After the introduction of sucrose in fruits and juices or glucose polymers in infant formula, it becomes apparent during infancy. At locus 7q34 on chromosome 7, the human maltase-glucoamylase gene (MGAM) can be found. Children with chronic diarrhea had a prevalence of 1.8 % for maltase-glucoamylase deficiency.

• Trehalase Deficiency - Trehalose, a disaccharide in mushrooms, yeast, and algae, is broken down by the trehalase enzyme. The human trehalase gene (TREH) is situated at locus 11q23 on chromosome 11. 8 % of the people in Greenland are said to have isolated trehalase deficiency.

What Are the Symptoms of Disaccharidase Deficiency?

The common symptoms of disaccharidase deficiency are

• Abdominal pain.

• Diarrhea.

• Nausea.

• Indigestion.

• Constipation.

• Poor weight gain.

• Flatulence.

• Irritable bowel syndrome - constipation and diarrhea subtype.

How Is Disaccharidase Deficiency Diagnosed?

Various tests are used to diagnose disaccharidase deficiency; they are

1. Breath Test

   • Procedure - The test substrate is consumed after a basal collection of exhaled breath and an overnight fast. For up to three hours, additional samples of exhaled breath are acquired at intervals of 30 minutes. A disaccharidase deficiency test result is considered positive if there is an increase of at least 20 ppm in hydrogen or 10 ppm in methane above the baseline.

   • Indicators for Diagnosis - Diarrhea or abdominal pain experienced during the test are supportive indicators of a good result. The benefit of this test is that it represents the small intestine's overall ability to absorb the substrate. The test's drawbacks include the time required and the fact that each sugar under consideration must be the subject of a separate investigation. A very small percentage of people do not create hydrogen or methane; hence this test will result in a false negative. Usually, during the test, these people show signs of pain or diarrhea, but there is no increase in the hydrogen or methane levels in the breath.

2. Lactose Intolerance Test (LTT)

   • Procedure - Serial blood glucose measurements are taken after ingesting lactose.

   • Indicators for Diagnosis - The LTT has a specificity range of 77 to 96 % and a sensitivity range of 76 to 94 %. Since the advent of breathalyzer tests, the LTT is seldom ever utilized.

3. Stool-Reducing Test - Sugars that were not absorbed can be found in the feces. Galactose, fructose, maltose, and lactose all react positively with Clinitest tablets (reducing sugars). Because of this, a positive test result indicates the presence of unabsorbed sugar in the stool without specifying which sugar it is. Due to earlier bacterial fermentation of the sugar in the colon, false negative tests may happen. Since they are non-reducing sugars or sugar alcohols, sucrose, lactulose, sorbitol, and mannitol cannot be detected by Clinitest tablets.

4. Osmotic gap

   • Procedure - The most accurate way to calculate the osmotic gap is to measure the electrolytes in the stool and use the formula gap=290- 2x(Stool Na+ + K+).

   • Indicators for Diagnosis - An elevated stool osmotic gap (>125 mOsm/kg) is often the outcome of diarrhea caused by a lack of disaccharidase. The osmotic gap does not pinpoint the offending sugar but indirectly indicates a disaccharidase deficit.

5. Fecal pH - A low fecal pH characterizes diarrhea brought on by the malabsorption of carbohydrates. A fecal pH of 5.3 in experimentally produced diarrhea implies that carbohydrate malabsorption is the primary cause of diarrhea. A pH of greater than 5.6 means that diarrhea is not exclusively caused by carbohydrate malabsorption.

6. Stool Electrophoresis - Unless the colonic bacterial flora has fully fermented the sugar, this test can identify a specific unabsorbed sugar in the feces. This test is expensive and time-consuming; hence it is rarely utilized.

7. Disaccharidase Assay - One small intestine biopsy sample can be used to determine the levels of disaccharidase enzymes. Only a few laboratories globally and in the United States offer the test. This test has the benefit of being able to measure all disaccharidases' activity directly, except trehalase. The drawback is that it necessitates an endoscopy and a tiny intestinal mucosa biopsy. Additionally, the test does not account for the small intestine's ability to absorb each sugar individually. Its results may be inaccurate in conditions with patchy intestinal mucosal abnormalities, such as celiac disease.

How Is Disaccharidase Deficiency Managed?

The various treatment for disaccharidase deficiency are

• Dietary Restriction - Disaccharidase, the enzyme that causes symptoms, must be eliminated from the diet. Due to the numerous undetected sources of these sugars in meals and pharmaceuticals, this therapy is only sometimes feasible. Additionally, a lack of calcium intake may result from completely excluding lactose-containing foods.

• Yogurt - Lactase-insufficient people may be able to handle yogurt, which is also a rich source of calcium. Due to slower stomach emptying, symptoms may be less severe if lactose is consumed with a high-fat meal. Drinking milk with meals and choosing whole milk or chocolate milk over skim milk helps lessen the symptoms of lactose intolerance, perhaps due to delaying stomach emptying. Alternately, adding lactase of microbiological origin to dairy products may be advised.

• Enzyme Supplementation - For those who have trouble absorbing lactose or sucrose, there are several enzyme supplements, including Lactaid and Sucraid, as well as fresh baker's yeast.

• Capsules - Take one to two capsules with milk or dairy products to treat lactase insufficiency; pre-treat milk with one to two tablets per quart of milk; 5 to 15 drops of liquid per quart of milk; one to three pills should be taken with meals. Infants and children up to 15 kg require 8500 international units (one mL) per meal or snack; children above 15 kg and adults require 17,000 international units (two mL) per meal or snack to treat sucrose deficit.

• A nutritional consultation can be helpful. Disaccharidase deficits that are either congenital or primary need lifelong care. Secondary disaccharidase deficiency may be temporary, and treatment may only be necessary while the source is dealt with and the gut lining is healing.

Conclusion

Disaccharidase deficiency's primary causes are unavoidable. However, genetic counseling and proactive advice may aid in the early detection of other patients when an index case is found. In addition, there are specific preventable secondary disaccharidase deficiency causes. For example, the prevalence of the disease has been demonstrated to be significantly reduced by using the rotavirus vaccination, which will also reduce the incidence of acquired disaccharidase deficiency. Similarly, maintaining a healthy diet during and after infectious gastroenteritis helps reduce long-term mucosal damage.