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Hereditary Fructose Intolerance - Causes, Symptoms, and Treatment

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Hereditary fructose intolerance is a hereditary autosomal recessive disorder. Read this article to know more.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At March 31, 2023
Reviewed AtMarch 31, 2023

Introduction

Hereditary fructose intolerance (HFI) is a hereditary disorder. The incidence rate of HFI varies somewhat among countries and ethnic groups. The reported cases of HFI are increasing because of increased sugar consumption in industrialized countries. HFI is now widely acknowledged that excessive fructose consumption, even in otherwise healthy people, may have several negative effects over time linked to metabolic syndrome. Hereditary fructose intolerance is found mainly in infants and young children. HFI is caused due to deficiency of enzymes that break down fructose-1-phosphate. It is characterized by nausea, vomiting, abdominal discomfort, and metabolic disorder. A metabolic disorder is an alteration in events of chemical reactions in our body essential to living. HFI is noticed in infants after feeding them sweetened milk formulae, solid foods, fruits, and vegetables. A completely fructose-free diet results in the disappearance of the symptoms in the patients. Sometimes, HFI can be unnoticed, and due to that, it remains undiagnosed and can be fatal. Severe cases of HFI can develop a progressive coma and even death.

What Is Hereditary Fructose Intolerance?

Fructose is found commonly in the food source. Fructose is six-carbon ketonic sugar found in sweetened milk formulae, solid foods, fruits, and vegetables. Hereditary fructose intolerance (HFI) is a genetic disorder that children carry from their parents. HFI can be fatal and cause liver, kidney, and progressive comma. HFI is caused due to mutation in the gene. The ALDOB gene is responsible for causing HFI.

What Are the Causes of Hereditary Fructose Intolerance?

Human liver aldolase's compromised function is the primary cause of the metabolic disorder known as hereditary fructose intolerance (HFI). HFI is an autosomal recessive severe disease found mainly in infants and young children that is due to a deficiency of the liver-specific B isoform of the fructose-1,6-bisphosphate aldolase. Aldolase is the isoenzyme that catalyzes fructose 1,6-bisphosphate (FBP) and fructose-1-phosphate. Aldolase A (ALDOA) in muscle, ALDOB in the liver, small intestine, and kidney, and aldolase C (ALDOC) in the brain are the three tissue-specific aldolase isoenzymes found in mammals. HFI is a hereditary disease. Hereditary disease is caused by genetic alteration and carried by infants from their parents. HFI is caused by a mutation (alteration in the gene) in the human ALDOB gene. The human ALDOB gene is located on chromosome 9. Therefore, the infants have the chance of HFI if the parents have mutated the ALDOB gene.

What Are the Signs and Symptoms of Hereditary Fructose Intolerance?

Patients with HFI can be asymptomatic for a long time and show symptoms at a later stage of their life. When people with HFI consume fructose and sucrose, fructose-1-phosphate builds up and causes acute and long-term symptoms. Symptoms start to manifest when infants are fed with sweetened milk formulae, solid foods, fruits, and vegetables. Symptoms such as nausea, vomiting, and severe metabolic abnormalities, including hypoglycemia, are noticed. Renal tubular acidosis, hypertransaminasemia, and hyperuricemia are the additional symptoms noticed in patients with HFI. Prolonged fructose intake leads to poor feeding, growth failure, jaundice, hepatomegaly, bleeding, and progressive liver damage, which may be fatal in some cases. Infants with severe HFI can develop a progressive coma and even death.

The following are the symptoms of HFI

  • Nausea.

  • Vomiting.

  • Jaundice (yellowing of skin, eyes, and nails).

  • Abdominal pain.

  • Lethargy.

  • Seizures (involuntary, sudden shaky movement of the limbs).

  • Mild mental retardation.

The following are the signs of HFI:

  • Hypoglycemia (low blood glucose level in the blood).

  • Lactic acidemia (accumulation of lactic acid in the body).

  • Hypophosphatemia (low phosphate level in the blood).

  • Hyperuricemia (high level of uric acid in the blood).

  • Hypermagnesemia (high level of magnesium in the blood).

  • Hyperalaninemia (deficiency of phenylalanine).

  • Renal tubular acidosis (a condition in which excretion capacity is decreased).

  • Hypertransaminasemia (presence of elevated transaminase level in the liver).

  • Hepatomegaly (liver enlargement).

  • Hemorrhage.

  • Liver damage.

How is Hereditary Fructose Intolerance Diagnosed?

Fructose-free diet can result in the disappearance of symptoms in patients with HFI. After the challenging weaning phase, HFI infants develop a self-protective aversion to foods that upsets their stomachs. Therefore, HFI might go unnoticed for a long period in individuals who follow an unintentionally self-imposed reduced fructose diet. HFI poses a hazard when fructose is consumed accidentally. Undiagnosed HFI persons who were exposed to fructose died as a result. Hereditary fructose intolerance is conventionally diagnosed by observing clinical symptoms upon fructose challenge. The amplification refractory mutation system (ARMS) was used to analyze the patients’ deoxyribose nucleic acid (DNA) for the presence of seven known HFI mutations.

The following are the investigations to diagnose hereditary fructose intolerance:

  • Liver Function Test (LFT) - Patients with HFI show abnormal LFT, having high levels of transaminase. It can indicate signs of liver damage in severe cases.

  • Blood Tests - Blood tests can show high bilirubin, magnesia, amino acids, and low glucose level, indicating HFI.

  • Urine Test - A urine test can show ketone bodies in the patient’s urine.

  • Biopsy - The biopsy of the liver can detect the signs of fructose ingestion and liver damage.

  • Molecular Analysis - Molecular analysis is a noninvasive method that analyses mutation in the ALDOB gene.

  • Polymerase Chain Reaction (PCR) - PCR helps in the detection and fine mapping of the new ALDOB deletion (mutation). The test was performed by real-time quantitative PCR.

How is Hereditary Fructose Intolerance Treated?

  1. The removal of potential sources of fructose is the treatment of the choice in the case of HFI.

  2. Patients with HFI should be hospitalized as soon as possible before the symptoms get worse.

  3. The administration of glucose intravenously can do the symptomatic treatment of HFI to stabilize the glucose level in the body.

  4. Supportive treatment for liver and kidney insufficiency is recommended.

  5. The treatment of metabolic acidosis should be done if present.

  6. The cornerstone of HFI treatment is the dietary restriction of fructose, sucrose, sucralose, and sorbitol.

  7. It is specifically suggested against using fructose-containing intravenous fluids, infant formula, and medications while a patient is hospitalized.

  8. Given that a diet must include fewer fruits and vegetables, daily supplementation with a "sugar-free" multivitamin is advised to avoid micronutrient deficits, particularly those involving water-soluble vitamins.

  9. After the diagnosis of HFI, regular monitoring of the liver and kidney is suggested.

  10. High-fructose corn syrup, honey, agave syrup, inverted sugar, maple-flavored syrup, molasses, palm or coconut sugar, and sorghum are examples of sugars that contain fructose, sorbitol, sucrose, sucralose, and polysorbate should be avoided in patients with HFI.

  11. Fructose-free diet and regular surveillance can treat the condition.

Conclusion

Hereditary fructose intolerance is a fatal autosomal recessive disease. Renal and hepatic failure could develop from untreated HFI. However, individuals with HFI can have a normal quality of life and life expectancy if recognized and treated before permanent organ damage develops. The vaccination against HFI can prevent infants from developing HFI. The concept of proper counseling to parents should be encouraged. Parents diagnosed with ALDOB genetic mutation should know they have 25 percent chance of developing HFI in their children. Abstinence from fructose can treat the symptoms of HFI. Proper diagnosis and treatment can cure and save the lives of infants.

Frequently Asked Questions

1.

How Is Hereditary Fructose Intolerance Inherited?

Hereditary fructose intolerance is passed down through generations in an autosomal recessive manner, necessitating the inheritance of two mutated gene copies, one from each parent, for the condition to manifest in an individual. If only one copy is inherited, the person is a carrier but does not typically experience symptoms.

2.

What Is the Relationship Between Aldolase B Deficiency and Hereditary Fructose Intolerance?

Aldolase B deficiency is the underlying cause of hereditary fructose intolerance. This deficiency prevents the breakdown of fructose in the liver, leading to a toxic accumulation of fructose-1-phosphate. This results in various symptoms and complications associated with hereditary fructose intolerance, such as hypoglycemia and liver damage.

3.

How Does Hereditary Fructose Intolerance Lead To Hypoglycemia?

Hereditary fructose intolerance leads to hypoglycemia due to the impaired breakdown of fructose in the liver. The deficiency of the aldolase B enzyme results in the accumulation of fructose-1-phosphate, which depletes the available phosphate in the liver. This disrupts gluconeogenesis, the process of generating glucose, leading to low blood sugar levels or hypoglycemia.

4.

What Should Be Done if a DNA Test Shows Hereditary Fructose Intolerance?

If a DNA test indicates the presence of hereditary fructose intolerance, it is crucial to seek advice from a healthcare professional or genetic counselor for further guidance and interpretation. They can provide guidance on managing the condition, creating a suitable diet plan, and monitoring for potential complications.

5.

How Does Jaundice Develop in Individuals With Hereditary Fructose Intolerance?

Jaundice can develop in individuals with hereditary fructose intolerance due to liver damage caused by the accumulation of toxic substances, such as fructose-1-phosphate. The liver's impaired function leads to the buildup of bilirubin, resulting in the yellowing of the skin and eyes characteristic of jaundice.

6.

Which Chromosome Is Affected by Hereditary Fructose Intolerance?

Hereditary fructose intolerance is caused by mutations in the ALDOB gene, which is located on chromosome 9. These mutations result in the deficiency of the aldolase B enzyme, leading to the development of hereditary fructose intolerance.

7.

Why Is Hereditary Fructose Intolerance Asymptomatic When Aldolase Is Missing in the Liver?

Hereditary fructose intolerance can be asymptomatic when aldolase is missing in the liver because the liver does not require aldolase B for its essential functions. Other metabolic pathways can compensate for the lack of aldolase B, allowing the liver to function normally despite the enzyme deficiency.

8.

What Are the Causes of Hereditary Fructose Intolerance?

Hereditary fructose intolerance is caused by mutations in the ALDOB gene, which encodes the aldolase B enzyme. These genetic mutations result in a deficiency or absence of functional aldolase B, leading to the inability to properly metabolize fructose and causing the symptoms of the condition.

9.

Does Fructose Intolerance Result in High Blood Sugar?

No, fructose intolerance typically does not result in high blood sugar. Instead, it often leads to low blood sugar levels or hypoglycemia. This is because the impaired metabolism of fructose in individuals with fructose intolerance disrupts gluconeogenesis, which is the process that generates glucose.

10.

What Substance Can Trigger Symptoms in Individuals With Hereditary Fructose Intolerance?

The substance that can trigger symptoms in individuals with hereditary fructose intolerance is fructose itself. When individuals with this condition consume foods or drinks containing fructose, it cannot be properly metabolized, leading to the accumulation of toxic byproducts and causing various symptoms associated with the condition.

11.

What Happens to Fructose After It Is Absorbed Into the Bloodstream?

After fructose is absorbed into the bloodstream, it is transported to the liver, where it should be metabolized by the aldolase B enzyme. However, in individuals with hereditary fructose intolerance, the deficient enzyme leads to the accumulation of fructose-1-phosphate, causing various symptoms and complications.

12.

Which Starches Are Safe for Individuals With Hereditary Fructose Intolerance?

For individuals with hereditary fructose intolerance, it is generally safe to consume starches that do not contain fructose. Starches such as potatoes, rice, corn, and wheat-based products are typically well-tolerated, as they do not contain high levels of fructose. Due to potential variations in individual tolerances, it is essential to consult with a healthcare professional or registered dietitian to receive personalized dietary recommendations regarding hereditary fructose intolerance.

13.

How Does Hereditary Fructose Intolerance Lead To Hypoglycemia?

Hereditary fructose intolerance leads to hypoglycemia by disrupting the normal process of gluconeogenesis. The deficiency of the aldolase B enzyme prevents the proper breakdown of fructose in the liver, leading to a decrease in the production of glucose and subsequently causing low blood sugar levels or hypoglycemia.

14.

What Are the Effects of Hereditary Fructose Intolerance on Individuals?

Hereditary fructose intolerance can cause various effects on individuals, including symptoms such as abdominal pain, nausea, vomiting, diarrhea, and bloating after consuming fructose. Untreated hereditary fructose intolerance can result in liver and kidney damage, hypoglycemia, growth retardation, and, in severe instances, cognitive impairment or even mortality.

15.

What Does It Mean to Be a Carrier of One Gene for Hereditary Fructose Intolerance?

Being a carrier of one gene for hereditary fructose intolerance means that an individual has inherited a single mutated gene for the condition from either one of their parents. As a carrier, they typically do not experience symptoms but have the potential to pass on the gene to their offspring.
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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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