OVERVIEW

What is hereditary fructose intolerance?

Hereditary fructose intolerance is a genetic disorder caused by a deficiency of the enzyme "fructose-1,6-bisphosphate aldolase."

This enzyme can be divided into three isoenzymes: a, b, and c, with type b fructose-1,6-bisphosphate aldolase being predominant in the liver, kidneys, and small intestine.

In children with this condition, the activity of fructose-1,6-bisphosphate aldolase in the liver ranges from complete absence to approximately 12% of normal levels.

Reduced activity of fructose-1,6-bisphosphate aldolase can lead to recurrent hypoglycemia-related symptoms and vomiting after consuming foods containing fructose, sucrose, or sorbitol. However, symptoms resolve immediately if intake is discontinued.

Hereditary fructose intolerance can sometimes be severe. Long-term or repeated consumption of foods containing fructose, sucrose, or sorbitol may result in growth retardation, intellectual disability, and liver or kidney dysfunction, such as acute liver failure or cirrhosis. In the most severe cases, it can lead to death.

Currently, there is no cure for hereditary fructose intolerance. The primary treatment is dietary control, avoiding foods and medications containing fructose, sucrose, or sorbitol. If hypoglycemia occurs, glucose should be administered for symptomatic relief.

How common is hereditary fructose intolerance?

It is rare. Since patients experience no issues if they avoid fructose, the incidence of this genetic disorder is difficult to estimate.

• International studies suggest a prevalence of 1/20,000 to 1/30,000, with some variation among ethnic groups.
• There are no specific prevalence data for China. Hereditary fructose intolerance was included in the National Rare Diseases List in 2018.

Is hereditary fructose intolerance the same as lactose intolerance?

No, they are different conditions.

• Lactose intolerance: Caused by a deficiency or low secretion of lactase, leading to incomplete digestion of lactose in breast milk or cow's milk and resulting in recurrent diarrhea. It is relatively common and often occurs in newborns and infants whose diet consists mainly of milk.

• Hereditary fructose intolerance: Caused by reduced activity of fructose-1,6-bisphosphate aldolase, making the body unable to metabolize fructose, leading to recurrent hypoglycemia and vomiting. It is rare.

SYMPTOMS

What are the common manifestations of hereditary fructose intolerance?

Children with hereditary fructose intolerance may experience metabolic abnormalities such as hypoglycemia, lactic acidosis, hypophosphatemia, hyperuricemia, hypermagnesemia, and hyperalaninemia after consuming fructose, sucrose, or sorbitol.

Symptoms include nausea, vomiting, abdominal pain, bloating, cold sweats, convulsions (limb twitching), and even fainting and shock.

• Newborns fed with formula immediately after birth often develop symptoms of acute liver failure, such as vomiting, diarrhea, dehydration, and shock, within 2–3 days.
• Breastfed infants typically show symptoms after introducing complementary foods containing sucrose or fructose, experiencing hypoglycemic symptoms like vomiting, abdominal pain, cold sweats, or even coma and convulsions within 30 minutes of feeding.

What severe consequences can hereditary fructose intolerance cause?

Long-term repeated consumption of foods containing fructose, sucrose, or sorbitol can lead to growth retardation, intellectual disability, and abnormal liver and kidney function in affected children, manifested as loss of appetite, diarrhea, failure to gain weight, hepatomegaly, jaundice, edema, and ascites.

In cases of short-term excessive intake, it may even result in death.

CAUSES

What is the cause of hereditary fructose intolerance?

Hereditary fructose intolerance is a genetic disorder caused by a defective gene that results in the deficiency of aldolase B enzyme in the body. This prevents the normal metabolism of ingested fructose into glucose for energy and also impairs the liver's gluconeogenesis, leading to reduced blood glucose levels and hypoglycemia.

In addition to fructose, consuming sucrose or sorbitol can also produce the same harmful effects.

How is hereditary fructose intolerance inherited?

Hereditary fructose intolerance follows an autosomal recessive inheritance pattern.

• If both parents are asymptomatic carriers of the defective gene, each child has a 1/4 chance of being affected regardless of gender. Among unaffected children, 2/3 will be carriers.

• If one parent is an asymptomatic carrier and the other is completely normal, none of the children will be affected, but half will be carriers.

• If one parent has hereditary fructose intolerance and the other is completely normal, all children will be carriers.

• If one parent has hereditary fructose intolerance and the other is a carrier, each child has a 1/2 chance of being affected regardless of gender. All unaffected children will be carriers.

• If both parents have hereditary fructose intolerance, all children will be affected regardless of gender.

DIAGNOSIS

How is hereditary fructose intolerance diagnosed?

If an infant repeatedly experiences hypoglycemia and vomiting after consuming fructose or sucrose, with symptoms disappearing within hours after stopping intake, doctors will strongly suspect hereditary fructose intolerance. However, further tests are needed for confirmation:

• Previously, doctors relied on liver biopsies or fructose tolerance tests for diagnosis, but these invasive procedures made widespread screening difficult.
• Currently, genetic testing can confirm hereditary fructose intolerance.

Which diseases is hereditary fructose intolerance easily confused with?

Hereditary fructose intolerance is often mistaken for congenital lactase deficiency, fat malabsorption, or protein malabsorption. Doctors typically differentiate it based on clinical manifestations and genetic testing.

TREATMENT

Which department should I visit for hereditary fructose intolerance?

Pediatrics or endocrinology.

How is hereditary fructose intolerance treated?

There is currently no cure for hereditary fructose intolerance. Long-term dietary control is necessary to prevent symptoms. The principle of dietary management is to avoid foods and medications containing fructose, sucrose, or sorbitol.

If symptoms occur due to accidental ingestion, leading to hypoglycemia, glucose therapy should be administered for symptomatic relief.

Does hereditary fructose intolerance require hospitalization?

Generally, hospitalization is unnecessary for hereditary fructose intolerance as long as foods and medications containing fructose, sucrose, or sorbitol are avoided in daily life. Hospitalization is only required in cases of severe hypoglycemia for intravenous glucose treatment.

DIET & LIFESTYLE

What should patients with hereditary fructose intolerance pay attention to in their diet?

Avoid foods containing fructose, sucrose, or sorbitol. Patients and their families can prepare a small notebook to record foods that are strictly prohibited and foods that can be safely consumed. Below are some references.

Strictly prohibited foods:

• Processed foods containing added sugar, honey, xylitol, aspartame, corn syrup, etc.;
• Chinese patent medicines containing lozenges, syrups, licorice, etc.;
• Vegetables such as carrots, sweet potatoes, pumpkins, and sweet corn;
• Almost all fruits.

Safe foods to consume:

• Dairy, meat, seafood, eggs, grains, nuts;
• Lettuce, asparagus, bamboo shoots, taro, potatoes, wild rice stems, water chestnuts, fern shoots, chicory, most leafy greens, bean sprouts, pea shoots, daylily, Chinese broccoli, peppers, bitter melon, various legumes, all mushrooms;
• Glucose, dextrin, maltose, most condiments;
• Tea, coffee, and alcoholic beverages (beer, dry red wine, liquor) without additives;
• Capsule or tablet medications, topical medications.

What should patients with hereditary fructose intolerance pay attention to in daily life?

No special precautions are needed in daily life; just maintain a healthy lifestyle.

How should patients with hereditary fructose intolerance schedule follow-up examinations?

The frequency of hospital follow-ups is generally determined by the doctor based on the patient's clinical condition. Regular monitoring of liver and kidney function, growth, and development is required.

Does hereditary fructose intolerance affect fertility?

Patients with hereditary fructose intolerance can conceive normally. Genetic counseling and prenatal diagnosis can help prevent the birth of affected offspring.

PREVENTION

How to prevent hereditary fructose intolerance?

There is currently no effective prevention method. However, expectant parents with a family history of this condition can undergo prenatal diagnosis to determine early whether their baby has inherited the disease and take appropriate interventions.

How can patients with hereditary fructose intolerance prevent complications?

Avoid consuming foods and medications containing fructose, sucrose, or sorbitol. If symptoms occur due to accidental intake, administer glucose immediately for symptomatic treatment.