Fructose Metabolism Defects - Symptoms, Diagnosis, and Treatment

Introduction:

Fructose is a type of simple sugar. It is an essential source of carbohydrates in the diet. Adults in Western societies currently consume about 100 g per day. It is found in honey, fruits, and many vegetables in its free form, and it is associated with glucose in the disaccharide sucrose in many foods and beverages. Sorbitol, found in various fruits and vegetables, is converted to fructose in the liver by sorbitol dehydrogenase. Fructose is primarily metabolized by fructokinase, aldolase B, and triokinase in the liver, renal cortex, and small intestinal mucosa. Aldolase B participates in the glycolytic-gluconeogenic pathway as well.

Fructose, unlike glucose, causes a slow rise in blood sugar levels. As a result, some doctors recommend fructose as a "safe" sweetener for people with type 2 diabetes. For women, the American Heart Association advises consuming no more than five teaspoons of added sugar daily, while men can consume upto nine teaspoons.

What Are The Different Fructose Metabolism Defects?

In the pathway of fructose metabolism, three inborn errors are known:

• Essential or benign fructosuria.

• Hereditary fructose intolerance.

• Fructose-1,6-bisphosphatase deficiency.

Essential fructosuria is a fairly innocuous condition characterized by fructose in the urine following the consumption of fructose-containing foods. Fructose may cause immediate gastrointestinal discomfort and hypoglycemia in patients with hereditary fructose intolerance (HFI); symptoms differ for each patient and rely on the ingested dose. When consumed in large quantities, fructose can cause liver and kidney failure, which can be fatal. Fructose-1,6-bisphosphatase (FBPase) deficiency is also commonly regarded as an inborn error of fructose metabolism, though it is technically a gluconeogenesis defect. It is characterized by hypoglycemia and lactic acidosis (either neonatally or later during fasting or induced by fructose) and can be fatal.

What Is Essential Or Benign Fructosuria?

Essential fructosuria occurs due to a deficiency of the enzyme hepatic fructokinase. It is a clinically benign condition characterized by the incomplete metabolism of fructose in the liver, leading to its excretion in urine. Fructokinase (or keto hexokinase) is the first enzyme in the liver that helps convert fructose to fructose-1-phosphate.

There are no clinical symptoms when fructose is either excreted unchanged in the urine or metabolized to fructose-6-phosphate via alternative pathways in the body, most frequently by hexokinase in adipose tissue and muscle.

• Cause: Essential fructosuria is a genetic condition that is autosomally recessive inheritance. Mutations in the KHK (keto hexokinase) gene, located on chromosome 2p23.3-23.2, are responsible. The prevalence of essential fructosuria is estimated to be one in every 30,000 people. However, because the condition is asymptomatic and harmless, it may be more common than is reported.

• Diagnosis: A positive routine test for reducing sugars in the urine usually helps to diagnose essential fructosuria. A glucose oxidase test must also be performed (with a negative result indicating essential fructosuria), as a positive test for reducing sugars is frequently the result of glucosuria secondary to diabetes mellitus. Fructose excretion in the urine fluctuates and is significantly influenced by dietary intake.

• Treatment: There is no treatment for essential fructosuria, and while the degree of fructosuria depends on dietary fructose intake, it has no clinical manifestations. The amount of fructose lost in urine is very small. Other errors in fructose metabolism are more serious clinically.

What Is Hereditary Fructose Intolerance?

Hereditary fructose intolerance is a fructose metabolism disorder caused by a lack of the enzyme aldolase B. Affected individuals are asymptomatic until they consume fructose, sucrose, or sorbitol. At this point, the aldolase B deficiency causes an accumulation of fructose-1-phosphate, which affects glycogenolysis, gluconeogenesis, and adenosine triphosphate regeneration. Because hereditary fructose intolerance is present at birth, most babies will experience symptoms when they start eating solid foods. It could be fatal if no treatment or lifestyle changes are implemented.

• Symptoms:

  • A strong dislike of sweets.

  • Growth delays.

  • Vomiting.

  • Jaundice.

  • Impaired physical development.

  • Hyperventilation.

  • Liver or kidney failure.

• Diagnosis: A doctor can use two tests to determine if the child has hereditary fructose intolerance. The first test is a liver biopsy, confirming an aldolase deficiency, indicating fructose intolerance. The second test is a feeding test, in which a doctor administers fructose via an IV (intravenous) needle. They then evaluate the body's reaction to the sugar. As these methods can be invasive, a DNA (deoxyribonucleic acid) test is better. This test can indicate whether or not a person has fructose intolerance, and it is safer than traditional testing.

• Treatment: Hereditary fructose intolerance is treated by eliminating fructose (found in sweet fruits), sucrose, and sorbitol from the diet. Severe hypoglycemia attacks are treated with intravenous glucose. In case of milder attacks, they are treated with glucose tablets, which anyone with hereditary fructose intolerance should keep on hand.

What Is Fructose-1,6-Bisphosphatase Deficiency?

Fructose-1,6-bisphosphatase deficiency is an inherited disorder in which the body cannot produce glucose properly. Glucose is the most common type of sugar in the blood and the primary energy source for the cells in the body. Fructose-1,6-bisphosphatase deficiency is an autosomal recessive disorder. Inherited genetic changes in the FBP1 gene cause Fructose-1,6-bisphosphatase deficiency. This deficiency, in turn, leads to impaired glucose production. Symptoms to focus on include symptoms of hypoglycemia.

Signs and symptoms

• Hunger.

• Irritability.

• Light-headedness.

• Fatigue.

• Lethargy.

• Seizures.

• Loss of consciousness.

• Trembling.

• Tachycardia.

• Hypertension.

Treatment

When FBPase deficiency is suspected, adequate intravenous or oral glucose should be administered. An IV bolus of 20 percent glucose should be administered to control hypoglycemia and acidosis, followed by a continuous infusion of glucose at high rates [10 to 12milligram per kg per minute (mg/kg/min) for newborns] and bicarbonate.

Fasting should be avoided during maintenance therapy, especially during febrile episodes. This entails frequent feeding, the intake of slowly absorbed carbohydrates (such as undercooked starch), and, if necessary, a gastric drip. In small children, it is also recommended to limit fructose, sucrose, and sorbitol, as well as fat to 20 to 25 percent of energy requirements and protein to 10 percent. Individuals with FBPase deficiency are healthy without any triggering effects that lead to metabolic decompensation, and no carbohydrate supplements are required.

Conclusion

Fructose metabolism defects refer to conditions in which fructose is not utilized and broken down properly in the body. Essential or benign fructosuria, hereditary fructose intolerance, and fructose-1,6-bisphosphatase deficiency are the three inborn defects of fructose metabolism. A doctor must be consulted if a person suspects fructose metabolism disorders to get a guided strategy for managing and treating fructose metabolism disorder.