Children's sugar malabsorption

　　One, Etiology

　　Sugar malabsorption can be divided into primary and secondary types:

　　1. Primary sugar malabsorption

　　In primary sugar malabsorption, congenital lactase deficiency, sucrase-isomaltase deficiency, and glucose-galactose malabsorption are all autosomal recessive genetic diseases that are rare in clinical practice. Apart from the sucrase-isomaltase deficiency, which can cause disease after adding sucrose to the diet, the rest all become symptomatic soon after birth. Biopsy of the small intestinal mucosa shows normal histology, but the activity of the corresponding disaccharidases is reduced. In glucose-galactose malabsorption, the activity of disaccharidases is all normal. Malabsorption is caused by the congenital deficiency of Na+-glucose, Na+-galactose carrier protein, and the child has good fructose absorption.

　　2. Secondary lactase deficiency and malabsorption of monosaccharides

　　It is more common in clinical practice, as lactase is distributed at the tip of the small intestinal villi. Any disease that can cause damage to the small intestinal mucosal epithelial cells and their brush border can lead to a deficiency in disaccharidases. Severe and widespread lesions can also affect the absorption of monosaccharides, such as acute enteritis (especially involving the upper part of the small intestine, such as rotavirus enteritis, Cryptosporidium infection, etc.), chronic diarrhea, protein-calorie malnutrition, immune deficiency disease, celiac disease, and small intestinal surgery injury, etc.

　　In the upper part of the jejunum, lactase mainly exists in the brush border of the apical epithelial cells of the villi, sucrase is more abundant in the body of the villi, and maltase is widely distributed in the intestines with the highest content. Therefore, when the small intestine is damaged, lactase is most likely to be affected and the recovery is the slowest, which is the most common in clinical practice; maltase is least affected, and sucrase deficiency is rare and only causes activity decline when the intestinal mucosa is severely damaged. At this time, the activity of lactase has often been affected, and it is often accompanied by the impairment of monosaccharide absorption.

　　Two, Pathogenesis

　　Carbohydrates ingested through the mouth include starch, lactose, and sucrose, which must be digested and hydrolyzed into monosaccharides before they can be absorbed by the small intestine. Starch includes both linear and branched chains, both being polymers of glucose. Amylase in saliva and the pancreas can hydrolyze starch, breaking it down into maltose (containing 2 molecules of glucose), maltodextrin (composed of several molecules of glucose), and dextrin. Dextrinase on the brush border of small intestinal epithelial cells (i.e., isomaltase) can hydrolyze dextrin molecules, while maltase can further hydrolyze maltose, ultimately breaking down all these sugars into glucose for absorption.

　　Lactose and sucrose are disaccharides. Lactase in the brush border of the small intestinal epithelium can decompose lactose into galactose and glucose; sucrase can decompose sucrose into fructose and glucose. Glucose and galactose can be actively absorbed in the small intestine, absorbed rapidly, and can reverse the concentration gradient, but energy is required. Fructose is mainly absorbed by carriers, and absorption cannot reverse the concentration gradient; while xylose (experimental) can only be absorbed by passive diffusion.

　　Sugar is absorbed relatively completely in the small intestine, but a small amount of unabsorbed sugar enters the colon and can be decomposed by intestinal flora (mainly Bifidobacteria, followed by Lactobacillus, etc.) and then absorbed.

　　1. Isotonic dehydration

　　Water and sodium are lost in proportion, so serum sodium remains within the normal range, and extracellular fluid can also maintain normal levels. Isotonic dehydration can cause a rapid decrease in extracellular fluid volume. Since the lost fluid is isotonic, the osmotic pressure of extracellular fluid remains basically unchanged, and intracellular fluid will not transfer compensatorily to the extracellular space.

　　2. Hypotonic dehydration

　　At this time, water and sodium are lost simultaneously, but sodium loss is greater than water loss. Serum sodium is below the normal range, and the extracellular fluid is in a hypotonic state.

　　3. Hypertonic dehydration

　　Water and sodium are lost simultaneously, but water loss is greater. Serum sodium is higher than the normal range, and the osmotic pressure of extracellular fluid increases. Severe dehydration can cause intracellular fluid to shift to the extracellular fluid gap, resulting in a decrease in both intracellular and extracellular fluid volume.

　　1. The unabsorbed sugar increases the osmotic pressure in the intestinal lumen, causing osmotic diarrhea.

　　2. Part of the sugar is lost in the stool, and part is fermented into organic acids and CO2, H2, methane, and other gases in the distal ileum and colon by bacteria. Some of these gases are absorbed and exhaled through the breath.

　　Therefore, children, especially infants and young children, often present with watery diarrhea (known as osmotic diarrhea) after eating food containing intolerant sugars. The stool contains foam and has an acidic and foul smell. The acidic stool can easily irritate the skin, causing diaper rash in infants. In severe cases, it can lead to erosion. Severe diarrhea often causes dehydration and acidosis, and electrolyte disturbances. Prolonged illness can lead to malnutrition. Some children may show abnormal hunger signs after correcting dehydration, and diarrhea symptoms can improve rapidly after fasting or removing intolerant sugars from the diet. This is one of the characteristics of the disease. Clinical symptoms in older children are often mild, and they may only present with bloating, increased flatulence, abdominal discomfort, intestinal colic, or hyperactive bowel sounds.

　　1. Strengthen prenatal care to prevent premature delivery.

　　6. Actively prevent and treat various intestinal diseases, especially infectious diseases and malnutrition, to prevent the occurrence of sugar malabsorption.

　　5. Regular physical examination: In order to achieve early detection, early diagnosis, and early treatment.

　　6. Strengthen the physique and improve self-immunity: Pay attention to the combination of work and rest, participate in more physical exercises, and eat more fresh fruits and vegetables rich in vitamins.

　　1. Blood routine and biochemical examination

　　Blood routine examination often shows macrocytic anemia, which can also be normocytic anemia or mixed anemia. Serum potassium, sodium, calcium, magnesium, phosphorus, and so on can be reduced. Plasma albumin, cholesterol, phospholipids, and prothrombin can also be reduced. In severe cases, serum folic acid, carotene, and vitamin B12 can also be reduced.

　　2. Screening test

　　1. Stool pH measurement

　　The pH of fresh stool in children with sugar malabsorption is often <6, and often below 5.5.

　　2. Stool reducing sugar test

　　Clinitest paper, modified Benedict's reagent, or lead acetate method can be used for the determination of reducing sugars. A concentration of ≥0.005 indicates poor sugar absorption.

　　Take 1 part of fresh stool, mix it with 2 parts of water, and then centrifuge it. Take 1ml of the supernatant, add 1 tablet of Clinitest reagent, and compare the color with the standard card to obtain the concentration of reducing sugars. A concentration of ≥0.5g/dl is positive, and a concentration >0.75g/dl in newborns is abnormal. The supernatant can also be added with Benedict's liquid and heated to measure reducing sugars.

　　Since sucrose is not a reducing sugar, add 1 part of stool to 2 parts of 1N HCl, heat it, and then take the supernatant. At this point, sucrose has been hydrolyzed into monosaccharides and can be measured for reducing sugars as described above. Since unabsorbed sucrose is often decomposed into reducing sugars by bacteria in the colon, it is usually not necessary to add HCl for hydrolysis first. However, if acid treatment is applied, the stool sugar is significantly higher than that without treatment, indicating poor absorption of sucrose in the child.

　　The stool contains other reducing substances, such as vitamin C, which can present false-positive results.

　　3. Breath hydrogen test

　　The method is sensitive, reliable, simple, and non-invasive, but requires a gas chromatograph to measure the hydrogen content in the exhaled breath. The human body itself cannot produce hydrogen, and the hydrogen in the exhaled breath is produced by the fermentation of sugar in the colon by bacteria. Most absorbable sugars for normal people can be completely absorbed before reaching the colon, while the fermentation and metabolism of unabsorbed sugars by intestinal bacteria is the only source of hydrogen in the human exhaled breath. This principle can be used to determine malabsorption of sugars in the small intestine.

　　Before and after intake of a test sugar, measure the hydrogen in the exhaled breath or 14CO2. If the exhaled hydrogen increases or the exhaled 14CO2 decreases after intake of the test sugar, it indicates poor absorption of the sugar. After fasting for 8 to 12 hours at night, measure the exhaled hydrogen as a baseline, then orally administer the test sugar at a dose of 2g/kg, not exceeding 50g at most. Some suggest reducing the dose to 0.25 to 0.5g/kg to reduce the symptoms of sugar intolerance. Collect the exhaled hydrogen content every half hour for a total of 2 to 3 hours. If the total hydrogen exceeds 20×10-6ppm compared to the fasting baseline, it can be diagnosed as poor absorption of the tested sugar. Antibiotics can suppress intestinal bacteria in children, which may lead to false-negative results.

　　四、小肠黏膜活检双糖酶活力测定

　　Fourth, determination of the activity of disaccharidases in small intestinal mucosal biopsy

　　It can be achieved by endoscopy or through the oral insertion of Crosby intestinal biopsy catheter, taking thin slices of intestinal mucosa under negative pressure, and performing histological examination and direct determination of various disaccharidase contents, which is particularly beneficial for the diagnosis of congenital sugar malabsorption. In sugar malabsorption, the activity of one or more disaccharidases is reduced.

　　Fifth, lactose tolerance test

　　Oral lactose 50g, blood glucose is measured every 30 minutes for 2 hours. In normal people, the blood glucose increases by more than 1.1mmol/L (20mg/dl) after taking lactose compared to fasting blood glucose; in lactase-deficient individuals, the blood glucose curve is low and flat, and lactose intolerance symptoms appear. However, blood glucose can be affected by many factors, and the results need to be combined with clinical findings for significance. Moreover, this test requires multiple blood draws, and it has been used less in recent years.

　　Sixth, determination of fecal sugar

　　Using chromatography, fecal sugar can be determined, and various types of sugar can be distinguished. Some also use lead acetate method to determine lactose in feces, these methods are of reference significance for diagnosis.

　　The diet for children with sugar malabsorption should avoid certain foods.
　　Most children only need to temporarily restrict lactose or give low lactose milk, such as fermented milk or low lactose奶粉, while some may need to restrict sucrose at the same time.
　　Within 2-3 weeks after the primary disease is restored, the function of most children's disaccharidases gradually recovers, and they can gradually return to normal diet.
　　Or low lactose diet is only used for children with protracted and chronic diarrhea that does not respond to long-term treatment, or for children with lactase deficiency detected. During the acute phase of pediatric enteritis, 60% to 70% of children have lactase deficiency, but as the acute enteritis recovers, the function of lactase also returns to normal quickly, so it is not necessary to use routine or low lactose diet during acute enteritis.

　　1. Treatment

　　1. Diet therapy

　　In theory, the treatment is simple, as long as intolerant disaccharides or monosaccharides are removed from the diet, it can be effective. However, there are many specific difficulties in actual implementation, such as how to find a suitable diet, how to maintain calories after sugar restriction, and how much sugar restriction can keep the child asymptomatic.

　　(1) Congenital glucose and galactose malabsorption: Soy milk without sugar can be given, supplemented with about 5% fructose feeding. After 2-3 years of age, the absorption function of the children is often restored, and they can tolerate small amounts of starch and lactose. However, to what extent the food containing starch and lactose can be increased requires the joint efforts of doctors and family members, and repeated tests.

　　(2) Sucrose-isomaltose malabsorption: It is necessary to limit the intake of sucrose from an early age to prevent symptoms, such as not adding sucrose to dairy products, glucose can be used instead, and it is also forbidden to take drugs containing syrup. With the growth of children, the strict restriction on sucrose can be gradually relaxed, but repeated tests are needed. Generally, there is no need to limit starch, because the component of branched-chain oligosaccharides containing 1.6 glycosidic bonds in starch is very little.

　　(3) Congenital lactase deficiency: Children should avoid lactose, including all types of milk and milk-containing foods. Infants can be fed with non-lactose milk powder, soy milk powder, or formula milk. They can also buy soy milk 100ml + glucose 5-10g according to the amount of milk needed for feeding. They can also make soy milk (500g soybeans, 4L water, grinding), and after making soy milk, add 0.5g of salt, 1.5g of calcium lactate, 10g of starch, and 30g of glucose per 500ml.

　　(4) Secondary disaccharide enzyme deficiency: Most children only need to temporarily limit lactose or provide low-lactose milk, such as fermented milk or low-lactose milk powder. Some may need to limit sucrose at the same time. After the primary disease recovers within 2-3 weeks, the function of disaccharide enzymes in most children gradually recovers, and they can then gradually return to normal diet. In acute enteritis, 60% to 70% of children have lactase deficiency, but the function of lactase quickly returns to normal with the recovery of acute enteritis, so routine application or low-lactose diet is not necessary during acute enteritis. Or low-lactose diet is only used for those with persistent and chronic diarrhea that does not respond to long-term treatment, or for children detected with lactase deficiency.

　　(5) Secondary monosaccharide malabsorption: It is less common, and it is necessary to remove all sugars from the diet. It is difficult to maintain sufficient calories during the course of the disease, and metabolic acidosis is difficult to control. At this time, it is often necessary to temporarily supplement a certain amount of calories by intravenous injection, and then gradually return to normal diet as the patient recovers.

　　2. Symptomatic treatment

　　Dehydration and electrolyte disorders caused by malabsorption of sugars should first be corrected by intravenous administration.

　　II. Prognosis

　　Primary lactase deficiency belongs to the category of physiological deficiency of type 2, and others are autosomal recessive hereditary diseases. After diagnosis and typing, dietary treatment should be given to achieve good results. Secondary malabsorption of sugars is common in clinical practice. In addition to thorough treatment of the primary disease, strengthening diet and symptomatic supportive treatment can promote the recovery of the condition. However, if severe water, electrolyte, acid-base balance disorders or severe infection occur, it can lead to the death of the child.