Aldolase B is an enzyme that helps the body process certain sugars. It is one of three types of aldolase enzymes found in vertebrates, each playing a role in breaking down molecules within cells. Aldolase B functions by catalyzing a reversible reaction that splits six-carbon fructose sugars into two three-carbon products. This enzyme is primarily active in the liver, kidneys, and small intestine.
Aldolase B’s Role in Sugar Metabolism
Aldolase B performs a specific biochemical function within sugar metabolism, particularly for fructose. When fructose is consumed, it is first converted into fructose-1-phosphate (F1P) by another enzyme called fructokinase. Aldolase B then acts on this F1P molecule, breaking it down into glyceraldehyde and dihydroxyacetone phosphate (DHAP).
These resulting three-carbon molecules, glyceraldehyde and DHAP, are then further processed. Glyceraldehyde can be phosphorylated to glyceraldehyde 3-phosphate (G3P). Both G3P and DHAP are intermediates that can enter the glycolytic-gluconeogenic pathway, where they are used to either produce energy or synthesize glucose. While aldolase B also participates in the breakdown of glucose, its role in fructose metabolism is more pronounced.
Hereditary Fructose Intolerance: The Primary Impact
A deficiency in aldolase B leads to a genetic condition known as Hereditary Fructose Intolerance (HFI). This disorder arises when the ALDOB gene, which provides instructions for making the aldolase B enzyme, has mutations. Mutations in the ALDOB gene cause HFI, often resulting in an enzyme with reduced or absent function. HFI is an autosomal recessive genetic disorder, meaning an individual must inherit two copies of the affected ALDOB gene, one from each parent, to develop the condition.
When functional aldolase B is lacking, fructose-1-phosphate (F1P) cannot be properly broken down and accumulates inside cells, particularly in the liver and kidneys. This buildup of F1P is toxic to cells and traps inorganic phosphate, preventing it from being returned to the general phosphate pool. The depletion of inorganic phosphate and adenosine triphosphate (ATP) stores disrupts normal cellular functions, including gluconeogenesis (glucose production) and glycogenolysis (glycogen breakdown). This disruption can lead to hypoglycemia, or low blood sugar, as well as liver damage and, in severe cases, liver cell death over time.
Recognizing and Diagnosing the Condition
Symptoms of Hereditary Fructose Intolerance emerge when infants or children begin consuming foods containing fructose, sucrose (table sugar), or sorbitol. These symptoms can include nausea, vomiting, abdominal pain, and diarrhea. Other manifestations include hypoglycemia, excessive sleepiness, irritability, and poor feeding, which can lead to a failure to thrive in infants. Prolonged exposure to fructose can result in more serious issues such as jaundice, an enlarged liver (hepatomegaly), and kidney damage. In severe cases, seizures and even coma may occur.
Diagnosis of HFI is primarily confirmed through genetic testing, which identifies mutations in the ALDOB gene. Historically, diagnosis involved enzyme assays from liver or small intestine biopsies, or cautiously performed fructose tolerance tests. However, fructose tolerance tests carry risks due to the potential for severe metabolic disturbances like hypoglycemia. Early diagnosis prevents serious complications by allowing for dietary measures. Dietary history, particularly the onset of symptoms after fructose intake, is also a significant indicator for suspected HFI.
Managing Hereditary Fructose Intolerance
Treatment for Hereditary Fructose Intolerance involves strict dietary elimination of all sources of fructose, sucrose, and sorbitol. This includes avoiding fruits, certain vegetables, honey, and many processed foods and drinks that use these sugars as sweeteners. Careful label reading is necessary, as sucrose and sorbitol are common ingredients.
With careful dietary management, individuals with HFI can lead healthy, normal lives, and symptoms resolve. Dietary changes should be overseen by a specialist dietitian to ensure adequate nutrition and to replace any vitamins that might be lacking due to dietary restrictions, such as vitamin C and folates. If the condition remains undiagnosed or is poorly managed, potential long-term complications can arise, including chronic liver disease, liver failure, or kidney disease. Early recognition and consistent adherence to the fructose-free diet improve the prognosis.