Aldolase B deficiency, or hereditary fructose intolerance (HFI), is a rare inherited metabolic disorder. It prevents the body from properly digesting fructose, a sugar in fruits, and its precursors like sucrose (table sugar) and sorbitol. The disorder stems from a deficient enzyme, leading to a toxic buildup of a substance in the body. HFI becomes apparent in infancy when these sugars are introduced into the diet, with a worldwide incidence of 1 in 20,000 to 1 in 30,000 people.
The Genetic Basis of the Deficiency
Hereditary fructose intolerance is caused by the body’s inability to produce a functional aldolase B enzyme, which is active in the liver, kidneys, and intestines. Normally, this enzyme breaks down fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate, which can then be used for energy. The instructions for the aldolase B enzyme are in the ALDOB gene.
Mutations in the ALDOB gene result in a defective enzyme that cannot metabolize fructose-1-phosphate. This leads to a toxic accumulation of fructose-1-phosphate in liver cells, causing cell death over time. The buildup also traps phosphate, which is needed for creating adenosine triphosphate (ATP), the cell’s main energy source, thereby disrupting energy production.
HFI is inherited in an autosomal recessive pattern, meaning an individual must inherit two mutated ALDOB genes, one from each parent. The parents, who each carry only one copy of the mutated gene, are considered carriers and do not show symptoms. For each pregnancy of two carrier parents, there is a 25% chance their child will have HFI.
Symptoms and Associated Health Risks
Symptoms of HFI appear shortly after consuming fructose, sucrose, or sorbitol, often when an infant is introduced to foods containing these sugars. Acute reactions include severe abdominal pain, bloating, vomiting, and excessive sleepiness. A dangerous acute symptom is profound hypoglycemia (low blood sugar), which can cause sweating, confusion, seizures, or coma.
If the condition is not diagnosed, continued fructose ingestion leads to chronic health problems as the toxic buildup of fructose-1-phosphate damages the liver and kidneys. This can result in an enlarged liver (hepatomegaly), jaundice, and progressive liver or kidney failure.
In children, this leads to a failure to thrive, with poor feeding, slow growth, and developmental delays. The metabolic disruptions can also cause high uric acid levels in the blood (hyperuricemia). Many people with undiagnosed HFI develop a natural aversion to sweets and fruits to avoid these symptoms.
The Diagnostic Process
Diagnosis of hereditary fructose intolerance begins with clinical suspicion, especially in an infant with symptoms like vomiting and hypoglycemia after consuming fructose. A detailed dietary history is taken, as symptoms consistently follow the ingestion of problematic sugars. A physical exam may reveal an enlarged liver or jaundice.
The safest and most definitive method for confirmation is molecular genetic testing. This blood test analyzes the ALDOB gene for known mutations, and finding two confirms the diagnosis. This non-invasive and accurate approach is the standard of care, as it can detect the most common mutations.
Past methods are now considered outdated and dangerous. A medically supervised fructose challenge test can cause a severe hypoglycemic reaction and is no longer recommended. A liver biopsy to measure enzyme activity has also been replaced by safer genetic testing.
Dietary Management and Lifestyle
Managing hereditary fructose intolerance requires a strict, lifelong elimination of all dietary fructose, sucrose, and sorbitol. Since there is no cure, this diet is the only way to prevent acute symptoms and long-term organ damage. With proper dietary control, individuals with HFI can live a normal, symptom-free life.
Foods to avoid include all fruits, fruit juices, honey, table sugar (sucrose), and high-fructose corn syrup, a common sweetener in sodas, baked goods, and candies. Some vegetables like asparagus and sweet potatoes must be limited, while others like spinach and potatoes are permitted. Sorbitol, a sugar alcohol in many “sugar-free” products, must also be eliminated because the body converts it to fructose.
Living with HFI requires careful reading of food and medication labels for hidden sugars. Working with a registered dietitian specializing in metabolic disorders is recommended. These professionals help create a balanced eating plan that provides all necessary nutrients while avoiding problematic sugars, ensuring long-term health.