What is Hereditary Fructose Intolerance?
Fructose is a type of sugar with 6 carbon atoms, and it’s commonly found in many foods. A condition called hereditary fructose intolerance comes with severe metabolic changes such as low blood sugar (hypoglycemia), overproduction of lactic acid in the body (lactic acidosis), and low phosphate levels in the blood (hypophosphatemia).
Hereditary fructose intolerance was first identified as an unusual response to fructose when a patient felt severe nausea, abdominal pain, and dizziness after consuming sugar and fructose. This reaction was documented by Chambers and Fratt in 1956. Over the next four to five years, scientists found out that the cause was a defect in a liver enzyme, and they figured out how the disease works inside the body (its pathophysiology).
What Causes Hereditary Fructose Intolerance?
Hereditary fructose intolerance is a genetic condition, specifically a disease that both parents must pass on the gene for it to be inherited (known as autosomal recessive). This condition is defined by the missing enzyme, Aldolase B. Enzymes are proteins that cause chemical reactions in the body. In this case, Aldolase B is responsible for breaking down fructose-1-phosphate, a sugar, into other compounds.
When there is no Aldolase B, a buildup of fructose-1-phosphate happens, which can harm the liver. This process also depletes the body’s supply of phosphate, a type of mineral that aids in energy production and storage. Since the fragmentation of fructose-1-phosphate is halted without Aldolase B, there’s also a decline in the breakdown of stored carbohydrates, known as glycogenolysis, for energy.
Lack of Aldolase B also disrupts the process of creating new glucose (a simple sugar used for energy), known as gluconeogenesis, because certain compounds aren’t formed.
Hyperuricemia, or high levels of uric acid (a chemical created when the body breaks down substances called purines) is a common symptom and is due to the increased breakdown of adenosine, a component of DNA. Other usual metabolic issues include high levels of magnesium in the blood (hypermagnesemia), buildup of lactic acid in the body (lactic acidosis), and excess levels of the amino acid alanine (hyperalaninemia).
Risk Factors and Frequency for Hereditary Fructose Intolerance
Hereditary fructose intolerance is a rare disease, so it’s difficult to determine how many people it affects. It’s estimated that somewhere between 1 in 20,000 to 1 in 60,000 people have the disease. It’s important to note that anyone can get this disease as it’s linked to an autosomal recessive inheritance, which means it affects both sexes equally. This disease happens due to different types of mutations.
Usually, doctors diagnose this disease a few months after a baby is born. This is often once the baby starts eating foods that contain fructose, which might lead to liver and kidney issues if left untreated. However, if the patient follows a proper diet, they can expect a normal lifespan.
- The disease is generally seen a few months after a child’s birth.
- It often becomes apparent when fructose-containing foods are introduced to the child’s diet.
- If it’s not treated, the disease can lead to significant issues with the liver and kidneys.
- However, with the right diet, a person with this disease can live a normal life.
People who carry a single copy of the mutated gene (heterozygotes) usually don’t show any symptoms of the disease. However, there are some reports that they might have high uric acid levels in their blood, which could make them more likely to develop gout.
Signs and Symptoms of Hereditary Fructose Intolerance
Hereditary fructose intolerance is a condition often seen in seemingly healthy infants. They might start to experience nausea, vomiting, difficulty eating, fatigue, and jaundice once new foods are introduced into their diet. It’s important to consider what the infant has been eating, since these symptoms are directly linked to the intake of fructose. If the child also shows signs of low blood sugar (hypoglycemia), low phosphate levels in the blood (hypophosphatemia), high uric acid levels (hyperuricemia), buildup of lactic acid in the body (lactic acidosis), and high magnesium levels (hypermagnesemia), it further suggests the presence of this condition. Also, during a physical checkup, the doctor might find stomach pain, enlarged liver (hepatomegaly), and slow growth.
Funnily enough, patients may start to avoid foods with sugar in them. Some patients are reported to have excellent dental hygiene because of their unique eating habits. The way this disease shows itself can vary. The typical case shows dramatic symptoms once foods containing fructose are brought into the diet. However, for patients whose defective gene still retains some function, symptoms may only appear when consuming large amounts of fructose.
- Nausea
- Vomiting
- Difficulty eating
- Fatigue
- Jaundice
- Low blood sugar (hypoglycemia)
- Low phosphate levels in the blood (hypophosphatemia)
- High uric acid levels (hyperuricemia)
- Buildup of lactic acid in the body (lactic acidosis)
- High magnesium levels (hypermagnesemia)
- Stomach pain
- Enlarged liver (hepatomegaly)
- Slow growth
Testing for Hereditary Fructose Intolerance
If your doctor suspects you may have hereditary fructose intolerance, they will likely start the diagnosis process with a urine test to look for reducing substances, which are compounds that react with certain chemicals to change color. Symptoms usually provide the first hint of this condition. The stick test for sugar in your urine (glucose dipstick test) will probably not show any glucose.
To make sure of the diagnosis, your doctor could recommend genetic testing or an exam of a small sample of your liver (a liver biopsy). The liver biopsy is used to measure the activity of an enzyme called aldolase. This enzyme performs a crucial role in breaking down fructose.
However, genetic testing is usually preferred. This is because it’s a more sensitive test, meaning it’s better at accurately detecting the disorder. Plus, it doesn’t require an invasive procedure like a biopsy. Genetic testing might involve sequencing a single gene, a multi-gene panel, or complete genetic testing (genomic testing).
Treatment Options for Hereditary Fructose Intolerance
The primary management for acute cases involves supportive care as other serious potential causes of the patient’s symptoms are identified and ruled out.
For hereditary fructose intolerance, the key approach is to avoid all food containing fructose, sucrose, and sorbitol. It could be beneficial to seek the guidance of a nutritionist. There are detailed lists of foods that contain fructose and recommended diet plans for patients available.
Patients might risk nutritional deficiencies due to lower consumption of fruits and vegetables in their diets. In this case, taking a daily multivitamin is advisable. Regular tests of the patient’s growth, kidney, and liver functions can be helpful, particularly if the patient is struggling to stick to a fructose-free diet.
It’s also useful to perform medical follow-ups using two tests: Transferrin Isoelectric Focusing (TfIEF) and monitoring the activity of an enzyme called Aspartylglucosaminidase (AGA). Both tests help in understanding the patient’s condition over time.
What else can Hereditary Fructose Intolerance be?
When a person experiences a sudden episode of hereditary fructose intolerance, it can look quite similar to other serious conditions. Some of these include blood poisoning (known as sepsis), a condition that disrupts normal blood clotting (disseminated intravascular coagulation), infectious liver disease (hepatitis), poisons entering the body (toxin ingestion), and certain genetic and metabolic diseases.[9]
Doctors should also consider metabolic diseases like galactosemia, urea cycle disorders, and disorders that affect how the body breaks down fats when they’re trying to find out what’s causing the symptoms.
It’s important to note that dietary fructose intolerance is different from hereditary fructose intolerance, even though they share similar symptoms such as feeling sick to the stomach (nausea), loose watery stool (diarrhea), and stomach pain after eating fructose. Dietary fructose intolerance is caused by faulty fructose transporters in the gut. The main difference between these two conditions is that, in dietary fructose intolerance, fructose is found in the stool, while in hereditary fructose intolerance, it’s found in the urine.
What to expect with Hereditary Fructose Intolerance
Patients who strictly follow a diet free of fructose usually have a very positive outlook. However, if a patient occasionally veers off the diet, they may face health complications related to their kidneys.
Possible Complications When Diagnosed with Hereditary Fructose Intolerance
Regularly consuming too much fructose can damage the liver, leading to poor liver function and even cirrhosis. This condition can also affect kidney health. If individuals do not adhere to dietary restrictions, they may experience slowed growth.
Key complications of this condition include:
- Effects on the central nervous system and intellectual abilities due to low blood sugar in acute episodes.
- Blood clotting disorders and acid levels imbalance during an acute episode which could harm multiple organs.
- High risk of severe infection (sepsis) caused by the Escherichia coli bacteria.
Preventing Hereditary Fructose Intolerance
Patients should be regularly reminded about the importance of not including fructose, a type of sugar, in their diet. Ideally, these reminders should come from a nutritionist who has experience in dealing with hereditary fructose intolerance, which is a condition that stops your body from properly breaking down fructose. Patients are also encouraged to always wear a medic alert bracelet. This bracelet can provide important information to medical staff in the event of an emergency. People who follow these dietary restrictions usually find that their health improves the most.
