Hereditary Fructose Intolerance - Causes, Symptoms, and Treatment

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.