What are the other Names for this Condition? (Also known as/Synonyms)

• ALDB - Aldolose B Deficiency
• Fructose 1 Phosphate Aldolase Deficiency
• Fructose Aldolase B Deficiency

What is Hereditary Fructose Intolerance? (Definition/Background Information)

• Hereditary Fructose Intolerance (HFI) is a genetic developmental disorder that prevents an individual from being able to digest fructose (a type of sugar commonly found in fruits, honey)
• The condition is onset at infancy and any intake of fructose leads to abdominal pain, nausea, vomiting, and low blood sugar. Continuous or repeated intake can cause serious damage to the kidneys and liver, leading to potentially fatal results
• Defective mutations of gene present on chromosome 9 are responsible for the disorder. HFI is autosomal recessive, implying that the gene defect has to be inherited from both parents to cause the condition
• Avoidance of fructose in the diet and addressing any liver damage, is the standard treatment mode that is followed

Who gets Hereditary Fructose Intolerance? (Age and Sex Distribution)

• The incidence of Hereditary Fructose Intolerance is estimated at 1 in 20,000-30,000 live births, around the world
• Both male and female sex population are uniformly affected
• Current research does not indicate any particular racial/ethnic predominance for Hereditary Fructose Intolerance

What are the Risk Factors for Hereditary Fructose Intolerance? (Predisposing Factors)

Hereditary Fructose Intolerance runs in the families and hence, children born in families with a medical history of the condition are at risk. Those having consanguineous partners/spouses have the greatest risk.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hereditary Fructose Intolerance? (Etiology)

• Hereditary Fructose Intolerance is caused by inheriting an autosomal recessive gene, which lies on chromosome 9 and is defective
• The problem gene (known as ALDOB), disturbs or changes the normal and physiologically programmed production of the enzyme aldolase B, resulting in a reduced or complete production failure of the enzyme

Autosomal Recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

• Aldolase B, found in the liver, is one of the key enzymes in metabolizing (chemically breaking down) fructose into various compounds, thereby generating energy for the body
• Since, both the quality and quantity of the enzyme produced are affected by improper gene functioning, a buildup of fructose and other associated compounds occurs in the liver. This causes progressive injury not only to the liver, but also to the kidneys and intestine, over time

What are the Signs and Symptoms of Hereditary Fructose Intolerance?

Signs and symptoms of Hereditary Fructose Intolerance are presented once the infant is started on artificially-sweetened formulaic food (or other mashed food, fruits, etc.). Repeated feeding of food containing fructose causes liver and kidney damage. The following are observed:

• HFI is asymptomatic in nature, before the intake of fructose
• Initial signs include diarrhea, vomiting, nausea, swollen abdomen with pain, hypoglycemia (low blood sugar). These are felt soon after consuming any food that contains fructose
• Baby has feeding problems; poor feeding is observed
• Baby does not gain weight or grow progressively, as much as a normal child would
• Liver damage signs include jaundice, enlarged liver (and spleen), chronic liver disease
• Epileptic seizures and coma may take place due to severe exposure to fructose

How is Hereditary Fructose Intolerance Diagnosed?

It is very important that Hereditary Fructose Intolerance be diagnosed as early as possible. This is to prevent serious harm from occurring, during the child’s most critical formative phase. Diagnostic tests for HFI that are performed on the newborn child, or on any affected individual include:

• Detailed physical examination; evaluation of the family medical history
• DNA test using a blood sample (it is non-invasive and safe for newborns)
• Liver biopsy to examine aldolase activity (this cannot be performed on an infant)
• Fructose tolerance test; by intravenously injecting fructose in a controlled manner (this cannot be performed on an infant)
• Kidney, liver function tests

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hereditary Fructose Intolerance?

Complications of Hereditary Fructose Intolerance could lead to fatalities. These include:

• Bleeding
• Gout
• Liver, kidney failure
• Complete dislike and avoidance of fruits and juices, containing fructose

How is Hereditary Fructose Intolerance Treated?

Management of Hereditary Fructose Intolerance is undertaken on a case-by-case, symptom basis. The measures considered are dependent upon the age of the individual, the disease stage, and acuity of the symptoms. These include:

• Avoidance of fructose (in any form) completely from the diet, for those in the initial stages of HFI. Fructose is substituted by glucose and maltose
• If liver damage has occurred from prolonged fructose exposure, then liver transplants may be performed

How can Hereditary Fructose Intolerance be Prevented?

• Currently there are no specific methods or guidelines to prevent Hereditary Fructose Intolerance genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for  treatment and prevention of inherited and acquired genetic disorders.

What is the Prognosis of Hereditary Fructose Intolerance? (Outcomes/Resolutions)

• Mild cases of Hereditary Fructose Intolerance are observed, when the disorder is detected early. This has a good prognosis. In such situations, a strict avoidance of fructose in the food helps most children/individuals with HFI
• Late detection of this condition in infants or children may cause serious injury to the liver and kidneys, due to continuous accumulation of fructose and their products. Removal of surplus fructose alone may not provide any relief; sometimes liver transplants may be required
• The outcome of an individual or a child is dependent upon:
  • The early/late diagnosis of the condition
  • Stage of the disorder (measured in terms of exposure level of the liver)
  • A quick removal of the damaging sugars from the body, and
  • Quality of the enzyme (aldolase B) present in the body
• Repeated intake of fructose inadvertently from any early stage, combined with a late discovery of the condition, may lead to potentially fatal outcomes

Additional and Relevant Useful Information for Hereditary Fructose Intolerance:

Hereditary Fructose Intolerance is many a time confused with a condition known as fructose malabsorption, which is a reduced absorption of fructose in the intestines leading to physiological problems. It is also known as dietary fructose intolerance, and is unrelated to HFI.