What is Fructose Intolerance?

Fructose is widely present in various fruits and vegetables, the highest content can reach 40% of dry weight, and is often used as an additive in food, so the human body ingests a large amount of fructose from its daily diet. After entering the human body, fructose is mostly metabolized in the liver, and only a small amount is metabolized by the renal tubules and the small intestine. The metabolic pathway of fructose is mainly catalyzed by three enzymes: fructose kinase first catalyzes fructose to produce l-phosphate fructose; l-phosphate fructose is then converted by aldolase to dihydroxyacetone phosphate and glyceraldehyde; glyceraldehyde is acted by glyceraldehyde , Phosphorylated into glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate and glyceraldehyde phosphate are intermediate metabolites of the glycolysis and gluconeogenesis pathways. Therefore, under the action of the above enzymes, about 50% of fructose is eventually converted to glucose, and the rest is glycogen and pyruvate. , Triglycerides and fats.

Fructose intolerance

Introduction to fructose intolerance

Fructose is widely present in various fruits and vegetables, the highest content can reach 40% of dry weight, and is often used as an additive in food, so the human body ingests a large amount of fructose from its daily diet. After entering the human body, fructose is mostly metabolized in the liver, and only a small amount is metabolized by the renal tubules and the small intestine. The metabolic pathway of fructose is mainly catalyzed by three enzymes: fructose kinase first catalyzes fructose to produce l-phosphate fructose; l-phosphate fructose is then converted by aldolase to dihydroxyacetone phosphate and glyceraldehyde; glyceraldehyde is acted by glyceraldehyde kinase , Phosphorylated into glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate and glyceraldehyde phosphate are intermediate metabolites of the glycolysis and gluconeogenesis pathways. Therefore, under the action of the above enzymes, about 50% of fructose is eventually converted to glucose, and the rest is glycogen and pyruvate. , Triglycerides and fats.

There are three types of obstacles to the fructose metabolism pathway caused by autosomal recessive inheritance:

Fructose kinase deficiency (also called idiopathic fructosuria) is caused by the lack of fructokinase in the liver, which prevents fructose from phosphorylation and cannot be further metabolized in the liver. Therefore, the fructose concentration in patients' blood is ingested fructose It increased significantly afterwards and was excreted from the urine without liver damage in this disease;

Hereditary fructose intolerance is caused by a deficiency of fructose diphosphate aldolase, which is the focus of this section;

Fructose-1,6-bisphosphatase deficiency, which is a catalytic enzyme in the glucose metabolism pathway, but it is customarily summarized in the deficiency of fructose metabolism.

Pathogenesis of fructose intolerance

Hereditary fructose intolerance is caused by a deficiency of fructose diphosphate aldolase. It is known that the molecular weight of the enzyme is 160,000 and is composed of 4 subunits; according to its catalytic activity, immune characteristics and distribution in different tissues, it can be divided into three types of isoenzymes A, B, and C. In the liver, kidney and small intestine, B-type fructose diphosphate aldolase is the main type, and its coding gene is located at 9q13 to q32, which is about 14500bp long. European data show that the three main point mutations of A149p, 174D and N334k are the main causes of fructose intolerance. The fructose diphosphate aldolase activity in the liver of children with this disease is completely absent from only about 12% of normal people. After ingesting fructose, a large amount of l-phosphate fructose accumulates in the cells. Accumulated fructose 1-phosphate can not only inhibit the fructose-1,6-bisphosphatase activity and cause the gluconeogenesis process to be blocked, but also because a large amount of inorganic phosphorus (Pi) is also surrounded by people, reducing blood phosphorus and ATP Regeneration is reduced. Both the accumulation of fructose 1-phosphate and the insufficient supply of ATP also hindered the release of glucose 1-phosphate from glycogen, thereby inhibiting the glycogen decomposition process and causing clinical symptoms of hypoglycemia. If you continue to feed with sucrose or fructose, it will cause liver cell damage in children. A long-term fructose-containing diet will cause liver cell necrosis, fat infiltration, bile duct hyperplasia and fibrosis, and even liver cirrhosis. The mechanism is not very good. Clearly, it may be due to the cytotoxic effect of fructose phosphate or related to the lack of ATP.

Clinical manifestations of fructose intolerance

The age of onset is related to the dietary ingredients used. Because most of the various milk formulas contain sucrose, neonatal children given artificial feeding immediately after birth often experience symptoms of acute liver failure such as vomiting, diarrhea, dehydration, shock, and bleeding tendency within 2 to 3 days. Breast-fed infants develop sucrose or fructose-containing complementary foods during their infancy, and symptoms of hypoglycemia such as vomiting, abdominal pain, cold sweats, and coma and convulsions occur within 30 minutes of feeding. Immediate appetite loss, diarrhea, weight loss, hepatomegaly, jaundice, edema, and ascites appear immediately. Some children will automatically refuse to eat because of uncomfortable symptoms after repeated consumption of "sweet foods" in infants. This protective behavior can make children grow up to adulthood. A small number of children may die from progressive liver failure due to undiagnosed treatment.

Fructose intolerance laboratory test

Check 1, blood biochemical examination in the emergence of acute symptoms, children should present hypoglycemia, at the same time blood phosphorus, blood potassium decreased transiently. Serum fructose, lactic acid, pyruvate, and uric acid increased.

In hypoglycemia, it is also seen that the serum insulin of the child is reduced, and the concentrations of glucagon, epinephrine and growth hormone are increased. With the change of these hormones, the plasma free fatty acids are significantly increased, which is different from normal people. Fructose-1,6-bisphosphatase deficiency (an autosomal recessive inheritance, its clinical manifestations closely resemble fructose intolerance, mainly liver enlargement) can cause hypoglycemia after eating fructose and when starving. Therefore, it is easy to be confused with glycogen accumulation disease, "ketogenic hypoglycemia" and this disease.

Detection of serum bilirubin, transaminase, and coagulation factors is helpful for the diagnosis and treatment of acute liver failure.

2. Urine biochemical examination should detect urine fructose in children with suspected acute illness. Children who continue to eat fructose often have renal tubular acidosis and Fanconi syndrome-like renal tubular reabsorption disorders. Therefore, urine pH, protein, amino acids, and bicarbonate should be tested.

3. Fructose tolerance test: Fructose, glucose, inorganic phosphorus, uric acid, and transaminase can be detected in the blood after rapid intravenous injection of 200 ~ 25mg / kg of fructose. This test should be performed several weeks after the condition is stable.

4. Enzymatic examination can be performed with liver, kidney or intestinal mucosal biopsy tissue, but it is not necessary for diagnosis.

Fructose intolerance treatment

1. Immediately terminate all foods containing fructose and sucrose.

2. Children with acute liver failure should be given active supportive treatment to correct hypoglycemia and electrolyte disturbances, and those with a tendency to bleeding can be given component transfusions.