HEREDITARY FRUCTOSE INTOLERANCE

Hereditary Fructose Intolerance — where a single dietary change (strict fructose avoidance) completely prevents liver failure, kidney damage, and hypoglycemic episodes that occur with each exposure to fructose, sucrose, or sorbitol.

Whole genome sequencing identifies all ALDOB variants — including the three common European mutations that account for 85% of alleles — providing the molecular diagnosis that replaces the dangerous intravenous fructose tolerance test.

ALDOB

About this condition

Hereditary Fructose Intolerance

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by pathogenic variants in ALDOB (aldolase B, chromosome 9q31.1). Aldolase B is the liver, kidney, and intestinal isoform of aldolase that cleaves fructose-1-phosphate during fructose metabolism. ALDOB deficiency causes fructose-1-phosphate accumulation after ingestion of fructose, sucrose, or sorbitol — trapping intracellular phosphate, inhibiting gluconeogenesis, and causing acute hypoglycemia, nausea, vomiting, and progressive liver and kidney damage. Carrier frequency is approximately 1 in 55-80 in European populations, with clinical prevalence of approximately 1 in 20,000-30,000.

HFI typically presents during weaning, when fruits, juices, and sucrose-containing foods are introduced to the infant's diet. Acute symptoms include nausea, vomiting, abdominal pain, and hypoglycemia after fructose-containing meals. Chronic fructose exposure produces hepatomegaly, jaundice, coagulopathy, renal tubular dysfunction, and failure to thrive. Many HFI patients develop a natural aversion to sweet foods and fruits — this self-protective behavior can lead to diagnostic delay, as the patient avoids the trigger without understanding why. Adults with undiagnosed HFI frequently report lifelong 'fruit intolerance' and are misdiagnosed with food allergies, IBS, or functional GI disorders.

Treatment is strict dietary avoidance of fructose, sucrose, and sorbitol — completely preventing all symptoms and tissue damage when maintained consistently. Hidden fructose sources (medications, IV fluids containing sorbitol, infant formula, processed foods) must be identified and eliminated. The historical diagnostic test — intravenous fructose tolerance test — carries risk of severe hypoglycemia and hepatic damage and has been largely replaced by molecular ALDOB genotyping. Three common ALDOB variants (p.Ala149Pro, p.Ala174Asp, p.Asn334Lys) account for approximately 85% of HFI alleles in European populations.

IV fluids and medications containing fructose, sucrose, or sorbitol can cause life-threatening hypoglycemia in HFI patients. Medical alert identification and complete medication review are essential after diagnosis.

Gene locus: ALDOB (9q31.1)

The historical fructose tolerance test is dangerous. Molecular ALDOB genotyping has replaced it as the diagnostic standard — safe, definitive, and simultaneously providing carrier status for family members.

Molecular diagnosis replaces the dangerous IV fructose challenge — ALDOB genotyping is both safer and more definitive

The intravenous fructose tolerance test required administering the exact substance that causes toxicity in HFI patients — producing predictable hypoglycemia, nausea, and hepatic injury, with rare reports of severe complications. Molecular ALDOB genotyping provides a definitive diagnosis from a blood sample without any fructose exposure. The three common European ALDOB variants (p.Ala149Pro, p.Ala174Asp, p.Asn334Lys) account for approximately 85% of disease alleles and are identified by whole genome sequencing alongside the remaining 15% of rare ALDOB variants that population-specific panels may miss.

Many adults with HFI are undiagnosed — labeled with 'food allergies' or IBS because they self-select away from sweet foods

HFI patients often develop a natural aversion to sweet foods, fruits, and juice in early childhood. By adulthood, they have unconsciously eliminated most dietary fructose and present with only intermittent GI symptoms from hidden fructose exposure. These patients are frequently diagnosed with food allergies, functional dyspepsia, or irritable bowel syndrome. Molecular diagnosis through whole genome sequencing — which evaluates ALDOB alongside thousands of other genes — can incidentally identify HFI in patients who were never specifically tested, finally explaining their lifelong dietary pattern.

Hereditary Fructose Intolerance — where a single dietary change (strict fructose avoidance) completely prevents liver failure, kidney damage, and hypoglycemic episodes that occur with each exposure to fructose, sucrose, or sorbitol.

Hereditary Fructose Intolerance

The historical fructose tolerance test is dangerous. Molecular ALDOB genotyping has replaced it as the diagnostic standard — safe, definitive, and simultaneously providing carrier status for family members.

Molecular diagnosis replaces the dangerous IV fructose challenge — ALDOB genotyping is both safer and more definitive

Many adults with HFI are undiagnosed — labeled with 'food allergies' or IBS because they self-select away from sweet foods

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