Hereditary fructose intolerance

Definition

Hereditary fructose intolerance is a metabolic disorder in which the small intestine cannot process fructose (fruit sugar) into a source of energy because of an enzyme deficiency that prevents fructose absorption.

Description

Fructose is a simple sugar found naturally in fruits, vegetables, and honey. Synthetic fructose (in the form of corn syrup) is used as a sweetener in many foods, including baby food, and sweetened beverages. Other simple sugars include glucose (the form in which sugar circulates in the blood) and galactose (produced by the digestion of milk). Simple sugars can be absorbed by the small intestine.

Digestion of food begins in the mouth, moves to the stomach, and then into the small intestine. Along the way, specific enzymes are needed to process different types of sugars. An enzyme is a substance that acts as a catalyst to produce chemical changes without being changed itself. People with fructose intolerance do not have the enzyme 1-phosphofructaldolase (also called aldolase B enzyme and fructose 1-phosphate aldolase). This enzyme is necessary for the absorption of fructose.

When people with fructose intolerance ingest fructose or sucrose (cane or beet sugar, table sugar), complicated chemical changes occur in the body due to the absence of the enzyme needed to process these sugars. The undigested fructose accumulates in the liver, kidneys, and small intestine, progressively causing damage that can lead to liver and kidney failure. The accumulated fructose interferes with the conversion of glycogen, the body's energy storage material, into glucose. As a result, the blood sugar falls to abnormal levels (hypoglycemia ).

An interesting feature of fructose intolerance is that children affected by the disorder develop a powerful protective aversion (feeling of intense dislike) to sweet-tasting foods and beverages. In addition, they have an exceptionally good record of dental hygiene, which is thought to be the result of diminished sugar and carbohydrate intake.

Demographics

Hereditary fructose intolerance is estimated to affect one in about 20,000 people. It is reported more frequently in the United States and northern European countries than in other parts of the world. It occurs with equal frequency in males and females.

Causes and symptoms

Causes

Fructose intolerance is an inherited disorder. Both the mother and father have the gene that causes the condition but may not have symptoms of fructose intolerance themselves. (This is called an autosomal recessive pattern of inheritance.)

Symptoms

The disorder is not apparent until the infant is fed formula, juice, fruits, or baby foods that contain fructose. Many soy-based formulas contain sucrose as a carbohydrate source. Initial symptoms include severe abdominal pain , vomiting that can lead to dehydration , and unexplained fever . Other symptoms include extreme thirst and excessive urination and sweating. There is also a loss of appetite and a failure to grow. Tremors and seizures caused by low blood sugar can occur. The liver becomes swollen, and the patient becomes jaundiced with yellowing of the eyes and skin. Left untreated, this condition can lead to coma and death.

When to call the doctor

If a child develops the following symptoms after he or she begins eating formula or solid food, the parent should contact the child's pediatrician:

• persistent or severe vomiting
• severe abdominal pain
• unexplained fever
• intolerance for fruits or avoidance of fruits/sucrose-containing foods
• extreme thirst
• excessive urination
• jaundice (yellowing of the eyes and skin)
• loss of appetite
• failure to grow
• unexplained weight loss

Early symptoms of hypoglycemia include:

• confusion
• dizziness
• feeling shaky or trembling
• hunger
• headache
• irritability
• fast heartbeat
• pale skin
• sweating
• sudden drowsiness, weakness, or fatigue

These symptoms can be treated by giving the child an oral glucose tablet, available from most pharmacies.

Symptoms of late hypoglycemia should be treated immediately. Parents should give the child a glucagon injection (a medication used in an emergency to increase blood glucose) and seek emergent treatment when the child has the following symptoms:

• inability to swallow
• numbness in mouth or tongue
• poor coordination
• poor concentration, confusion
• unconsciousness

When hypoglycemia is severe, it can lead to convulsions and coma. The child's doctor can advise the parents on how to manage the child's blood glucose levels to avoid hypoglycemic reactions as much as possible.

Diagnosis

The diagnosis includes a physical exam and evaluation of the child's family medical history. A family history of fructose intolerance may suggest a genetic predisposition to the disease. Several gene mutations causing hereditary fructose intolerance have been identified. Genetic testing with DNA analysis may be available to identify one of the common gene mutations that lead to this disorder. Positive results of the DNA test and the presence of clinical symptoms can serve as strong indicators of the condition. However, negative results are not a guarantee that the person does not have hereditary fructose intolerance.

Urine tests can be used to detect fructose sugar in the urine. Blood tests can also be used to detect hyperbilirubinemia and high levels of liver enzymes and uric acid in the blood. A liver biopsy may be performed to test for levels of enzymes present (aldolase assay) and to evaluate the extent of damage to the liver. A fructose tolerance test may also be used to confirm fructose intolerance. In this test, a dose of fructose is given to the patient in a well-controlled hospital or clinical setting. This test should only be performed on an asymptomatic patient. Both the biopsy and the fructose tolerance test are very risky, particularly in infants who are already sick.

Treatment

With early diagnosis, fructose intolerance can be successfully treated by eliminating fructose, sucrose, and sorbitol from the diet (less than 40 mg/kg per day). Sorbitol is an artificial sweetener found in many sugar-free products, such as sugarless gum or diet foods. Patients usually respond favorably within a few weeks and can make a complete recovery if fructose-containing foods are avoided. Early recognition and treatment of the disorder is important to avoid damage to the liver, kidneys, and small intestine.

Early symptoms of hypoglycemia can be treated with oral glucose tablets or gel, available at most pharmacies. The doctor can provide more information about how to manage a hypoglycemic reaction, as well as how to monitor the child's blood glucose levels using a blood glucose meter to prevent a hypoglycemic reaction. Severe hypoglycemia should be treated with a glucagon injection to increase the blood glucose level. In some cases, the child may need an intravenous glucose solution, given in the hospital.

Children with this condition should be managed by a medical specialist in biochemical genetics or metabolism, as well as a registered dietitian who can provide nutrition support and information.

Nutritional concerns

It is important for the child to avoid fructose, sucrose, and sorbitol sources and yet maintain proper nutrition. A registered dietitian can work with the parents and child to identify and avoid fructose and sucrose foods and beverages. This is very important, since many unsuspected food sources, such as potatoes when prepared a certain way, are significant sources of fructose. The dietitian can provide instructions for reading food and medication labels to detect these problem-causing substances. Regular follow-up appointments with a registered dietitian should be part of the child's overall treatment program.

Prognosis

There is no cure for hereditary fructose intolerance, since the enzyme needed to process fructose is missing at birth. The prognosis depends on how soon the diagnosis is made and how soon fructose and sucrose are eliminated from the child's diet. If the condition is not recognized and the diet is not well controlled, death can occur in infants or young children. With a well-controlled diet, the child will thrive and develop normally. In the absence of liver damage, the child's life expectancy is normal. Most of the damaging effects of the disorder can be prevented by strictly following the fructose-free diet.

Prevention

Carriers of the gene for hereditary fructose intolerance can be identified through DNA analysis. Anyone who is known to carry the disorder or who has the disorder in his or her family may benefit from genetic counseling. At-risk individuals can be assisted with family planning and reproductive decisions.

Nutritional concerns

To prevent complications from this disorder, parents should take the following steps:

• work with a registered dietitian to facilitate specific dietary changes
• carefully read food labels to identify and avoid dietary sources of fructose and sucrose
• maintain a regular follow-up schedule with the child's metabolic specialist

Parental concerns

Fructose intolerance can be a life-threatening condition if strict dietary guidelines are not followed. If the diet is relaxed, the child may fail to grow normally or may develop liver or kidney complications.

KEY TERMS

Aldolase B —Also called fructose 1-phosphate aldolase, this chemical is produced in the liver, kidneys, and brain. It is needed for the breakdown of fructose, a sugar found in fruits, vegetables, honey, and other sweeteners.

Digestion —The mechanical, chemical, and enzymatic process in which food is converted into the substances suitable for use by the body.

DNA —Deoxyribonucleic acid; the genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.

Enzyme —A protein that catalyzes a biochemical reaction without changing its own structure or function.

Hyperbilirubinemia —A condition characterized by a high level of bilirubin in the blood. Bilirubin is a natural byproduct of the breakdown of red blood cells, however, a high level of bilirubin may indicate a problem with the liver.

Lactose —A sugar found in milk and milk products.

Liver biopsy —A surgical procedure where a small piece of the liver is removed for examination. A needle or narrow tube may be inserted either directly through the skin and muscle or through a small incision and passed into the liver for collection of a sample of liver tissue.

Metabolism —The sum of all chemical reactions that occur in the body resulting in growth, transformation of foodstuffs into energy, waste elimination, and other bodily functions. These include processes that break down substances to yield energy and processes that build up other substances necessary for life.

Nutrient —Substances in food that supply the body with the elements needed for metabolism. Examples of nutrients are vitamins, minerals, carbohydrates, fats, and proteins.

Sugars —Those carbohydrates having the general composition of one part carbon, two parts hydrogen, and one part oxygen.

Preliminary evidence suggests that parents of a child with this disorder, and other carriers of the mutant gene, may have an increased risk for gout. Gout is a form of arthritis caused by excess uric acid in the body and uric acid crystals in the joints.

Resources

BOOKS

Brostoff, Jonathon, et al. Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment. Rochester, VT: Inner Traditions International, 2000.

David, T. J. Food and Food Additive Intolerance in Childhood. Oxford, UK: Blackwell's Publishing, 2002.

Emerton, Victoria. Food Allergies and Intolerance: Current Issues and Concerns. Cambridge, UK: Royal Society of Chemistry, 2002.

Emsley, John, et al. Was It Something You Ate? Food Intolerance: What Causes It and How to Avoid It. Oxford, UK: Oxford University Press, 2002.

Williams, Sue Rodwell, and Eleanor Schlenker. Essentials of Nutrition and Diet Therapy, 8th ed. Philadelphia: Mosby, 2002.

ORGANIZATIONS

American College of Gastroenterology (ACG). PO Box 3099, Alexandria, VA 22302. Web site: <www.acg.gi.org/patientinfo>.

National Center for Biotechnology Information. U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894. Web site: <www3.ncbi.nlm.nih.gov>.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 2 Information Way, Bethesda, MD 20892–3570. Web site: <www.niddk.nih.gov>.

National Institutes of Health. National Institute of Diabetes, Digestive, and Kidney Diseases. Building 31, Room 9A04, 31 Center Drive, Bethesda, MD 20892–2560. Web site: <www.nih.gov>.

WEB SITES

"Frequently Asked Questions [about fructose intolerance]." HFI Laboratory at Boston University. Available online at <www.bu.edu/aldolase/HFI> (accessed November 19, 2004).

Stewart, Douglas R. "Hereditary Fructose Intolerance." U.S. National Library of Medicine, August 19, 2003. Available online at <www.nlm.nih.gov/medlineplus/ency/article/000359.htm> (accessed November 19, 2004).

Altha Roberts Edgren
Angela M. Costello

Hereditary Fructose Intolerance

Definition

Hereditary fructose intolerance is an inherited condition where the body does not produce the chemical needed to break down fructose (fruit sugar).

Description

Fructose is a sugar found naturally in fruits, vegetables, honey, and table sugar. Fructose intolerance is a disorder caused by the body's inability to produce an enzyme called aldolase B (also called fructose 1-phosphate aldolase) that is necessary for absorption of fructose. The undigested fructose collects in the liver and kidneys, eventually causing liver and kidney failure. One person in about 20,000 is born with this disorder. It is reported more frequently in the United States and Northern European countries than in other parts of the world. It occurs with equal frequency in males and females.

Causes and symptoms

Fructose intolerance is an inherited disorder passed on to children through their parents' genes. Both the mother and father have the gene that causes the condition, but may not have symptoms of fructose intolerance themselves. (This is called an autosomal recessive pattern of inheritance.) The disorder will not be apparent until the infant is fed formula, juice, fruits, or baby foods that contain fructose. Initial symptoms include vomiting, dehydration, and unexplained fever. Other symptoms include extreme thirst and excessive urination and sweating. There will also be a loss of appetite and a failure to grow. Tremors and seizures caused by low blood sugar can occur. The liver becomes swollen and the patient becomes jaundiced with yellowing of the eyes and skin. Left untreated, this condition can lead to coma and death.

Diagnosis

Urine tests can be used to detect fructose sugar in the urine. Blood tests can also be used to detect hyperbilirubinemia and high levels of liver enzymes in the blood. A liver biopsy may be performed to test for levels of enzymes present and to evaluate the extent of damage to the liver. A fructose-loading test where a dose of fructose is given to the patient in a well-controlled hospital or clinical setting may also be used to confirm fructose intolerance. Both the biopsy and the loading test can be very risky, particularly in infants that are already sick.

Treatment

Once diagnosed, fructose intolerance can be successfully treated by eliminating fructose from the diet. Patients usually respond within three to four weeks and can make a complete recovery if fructose-containing foods are avoided. Early recognition and treatment of the disease is important to avoid damage to the liver, kidneys, and small intestine.

Prognosis

If the condition is not recognized and the diet is not well controlled, death can occur in infants or young children. With a well-controlled diet, the child can develop normally.

Prevention

Carriers of the gene for hereditary fructose intolerance can be identified through DNA analysis. Anyone who is known to carry the disease or who has the disease in his or her family can benefit from genetic counseling. Since this is a hereditary disorder, there is currently no known way to prevent it other than assisting at-risk individuals with family planning and reproductive decisions.

KEY TERMS

Aldolase B— Also called fructose 1-phosphate aldolase, this chemical is produced in the liver, kidneys, and brain. It is needed for the breakdown of fructose, a sugar found in fruits, vegetables, honey, and other sweeteners.

Hyperbilirubinemia— A condition where there is a high level of bilirubin in the blood. Bilirubin is a natural by-product of the breakdown of red blood cells, however, a high level of bilirubin may indicate a problem with the liver.

Liver biopsy— A surgical procedure where a small piece of the liver is cut out for examination. A needle or narrow tube may be inserted either directly through the skin and muscle or through a small incision and passed into the liver for collection of a sample of liver tissue.

Resources

ORGANIZATIONS

National Institutes of Health. National Institute of Diabetes, Digestive and Kidney Diseases. Building 31, Room 9A04, 31 Center Drive, Bethesda, MD 20892-2560. (301) 496-3583.

OTHER

"What Is Hereditary Fructose Intolerance?" Hereditary Fructose Intolerance & Aldolase Homepage. 〈http://www.bu.edu/aldolase〉.