What is Fructose-1-Phosphate Aldolase Deficiency?
Hereditary fructose intolerance (HFI) is a genetic disorder where the body can’t break down fructose properly due to a lack of a specific enzyme called aldolase B. It makes fructose-1-phosphate, a type of sugar, accumulate in the liver and kidneys. This condition usually begins showing symptoms when a baby is 4-6 months old and starts eating solid foods. It is a “recessive” disorder, which means that a child must inherit the faulty gene from both parents to have the condition. If both parents are carriers, there is a 25% chance that their child will have HFI.
The main way to manage HFI is by carefully controlling the diet to avoid foods containing fructose, sorbitol (a sugar substitute), and sucrose (table sugar). If individuals with this condition are able to maintain a strict diet, they can expect to live a normal lifespan. However, it’s very important to adhere to the diet to prevent damaging build-up of fructose in the body’s liver and kidneys.
What Causes Fructose-1-Phosphate Aldolase Deficiency?
Hereditary Fructose Intolerance (HFI) is a condition caused by a lack of a specific enzyme known as aldolase B. This enzyme is found in the liver, kidneys and the lining of the intestines, and it has a crucial role in breaking down and metabolizing a sugar called fructose.
The enzyme essentially works by breaking down more complex sugar compounds such as fructose-1-phosphate and fructose-1, 6-bisphosphate into simpler molecules that our bodies can use.
The gene responsible for creating aldolase B is located on a part of our DNA known as chromosome 9q22. There are a variety of mutations (changes) to this gene that have been identified, with the most common being A150P, A149P, and A174D.
The extent of the disease varies from person to person, depending on the level of activity of the aldolase B enzyme. Some people may not even realize that they suffer from this condition because they have unintentionally limited their intake of foods containing fructose.
Risk Factors and Frequency for Fructose-1-Phosphate Aldolase Deficiency
Hereditary Fructose Intolerance (HFI) is a condition that is passed down through families and affects both males and females equally. It’s estimated that about 1 in 20,000 births in the United States and 1 in 26,100 live births in Europe are affected by this disease.
Signs and Symptoms of Fructose-1-Phosphate Aldolase Deficiency
It’s crucial to understand a patient’s eating habits when diagnosing this condition. Symptoms typically appear in a baby around 4 to 6 months, when solid foods are first introduced. These can include frequent vomiting, bloating, diarrhea, a yellow tint to the eyes (a condition known as jaundice), an enlarged liver, and slow growth rates in infants. The severity of symptoms can depend on the activity of an enzyme called aldolase B. More often, these individuals are reluctant to eat foods rich in fructose and sucrose. It’s worth noting that some cases can go unnoticed for a long time.
People who carry the gene but don’t have the condition (known as heterozygous individuals or carriers) usually don’t show any symptoms. However, in some cases, high levels of uric acid (hyperuricemia) can be seen, which increases the risk of suffering from a type of arthritis called gout.
Testing for Fructose-1-Phosphate Aldolase Deficiency
HFI, or Hereditary Fructose Intolerance, is typically diagnosed based on certain symptoms and changes in the body’s metabolism, which are usually observed after a person eats foods containing fructose, sucrose, or sorbitol. These foods can trigger a reaction in people with HFI.
The Fructose Tolerance Test (FTT) is a standard medical test to diagnose HFI. Despite its utility, it’s not routinely used due to some of its potential side effects like low blood sugar (hypoglycemia) and low phosphate levels in the blood (hypophosphatemia). These are especially seen in adults. Furthermore, it can be challenging to administer the test to infants and children.
There are other options too. One involves genetic testing for changes in the ALDOB gene. This method is non-invasive, meaning it doesn’t require surgery or any physically intrusive procedure. This test is helpful because mutations in the ALDOB gene are known to cause HFI.
An invasive method of diagnosing HFI is through a liver biopsy. This test involves taking a small sample of liver tissue to look for aldolase B activity, since decreased activity of this enzyme is associated with HFI. But, being an invasive procedure, it’s usually done only when other non-invasive tests aren’t conclusive.
Treatment Options for Fructose-1-Phosphate Aldolase Deficiency
In a medical emergency, a patient may show signs of tiredness, experience seizures, enter a coma, or show signs of liver and kidney failure. To manage these symptoms, medical professionals will need to take several measures. They’ll give the patient glucose (a type of sugar) through an IV to support the body’s energy needs, rectify any imbalance in body’s acid levels, and provide supportive care. This situation requires a team of specialist doctors working together.
For people with a condition known as hereditary fructose intolerance (HFI), maintaining a specific diet is the key to treatment and preventing severe symptoms. They need to steer clear of fluids that contain fructose, a type of sugar. Because this diet restricts certain food groups, there’s a risk of missing out on important vitamins and minerals. To prevent this, people with HFI can take daily multivitamins, particularly those with folate and vitamin C.
What else can Fructose-1-Phosphate Aldolase Deficiency be?
There are multiple conditions that could lead to similar symptoms, such as:
- Infectious hepatitis, sepsis, or disseminated intravascular coagulation (a condition that causes blood clots through the body)
- Autoimmune liver disease
- Neonatal hemochromatosis (a condition in newborns leading to liver damage)
- Poisoning caused by ingesting toxic substances
- Alpha-1-antitrypsin deficiency (a condition affecting the lungs and liver)
- Tyrosinemia (a genetic disorder affecting how the body processes the protein building block, tyrosine)
- Galactosemia (a condition preventing the proper breakdown of galactose, a sugar)
- Urea cycle disorders (conditions affecting the removal of waste from the body)
- Citrin deficiency (a condition affecting protein metabolism)
- Fatty acid oxidation disorders, such as MCAD deficiency, VLCAD deficiency, and LCHAD deficiency (which negatively affect the body’s ability to break down certain fats)
- Maple syrup urine disease (a genetic disorder impeding the body’s ability to process certain amino acids)
- Wilson disease (a condition leading to a buildup of copper in the body)
- Glycogen storage disease (GSD, a condition preventing the proper storage and use of glycogen, a form of glucose)
- Disorders causing a decrease in mitochondrial DNA (needed to produce energy in cells)
- Transaldolase deficiency (a rare genetic disorder)
- Congenital disorders of glycosylation (a group of conditions affecting the way cells process certain proteins and fats)
What to expect with Fructose-1-Phosphate Aldolase Deficiency
The outlook for fructose intolerance is generally very good, as long as the person strictly sticks to the recommended diet. If the condition is identified early and managed promptly, the affected individual can have a normal mental development and live a normal life span.
Possible Complications When Diagnosed with Fructose-1-Phosphate Aldolase Deficiency
Not following a prescribed diet can result in serious health problems. These include:
- Severe hypoglycemia that might lead to a coma
- Lactic acidosis – a buildup of acid in your body
- Liver dysfunction
- Kidney dysfunction
- Abnormalities in the body’s metabolic processes
Preventing Fructose-1-Phosphate Aldolase Deficiency
For patients diagnosed with this specific disease, it’s critical that they and their families understand how to properly manage it, particularly by sticking to a specific diet. Recognizing and starting treatment early for this disease can greatly improve the patient’s brain development. If a family has been proven to carry a change (mutation) in a gene called ALDOB, it’s highly suggested they seek genetic counseling. This type of advice can help them understand what this gene change can mean for their health and any future children’s health.