Hereditary fructose intolerance

Autosomal recessive inborn error of fructose metabolism due to aldolase B deficiency; fructose (or sucrose) ingestion triggers toxic fructose-1-phosphate accumulation → severe hypoglycemia and potential organ failure.

• Rare but potentially lethal if unrecognized—infants can have seizures or liver failure when fed fructose. Early diagnosis allows simple diet changes to prevent death or disability, making HFI a classic high-yield pediatric metabolic disorder.

• Healthy newborn (breast milk only) until ~6 months; after introduction of fruit juices, baby develops vomiting, sweating/tremors (hypoglycemia), lethargy, and even seizures shortly after feeding. Continued fructose intake causes jaundice, hepatomegaly, and failure to thrive.
• Undiagnosed older infants/children may show a strong aversion to sweets (they refuse fruits, candy) due to learned intolerance, and may present with growth restriction and signs of liver or kidney dysfunction if fructose exposure persists.

1. Clue in history: infant was fine with breast milk (lactose) but got sick when fruits or sucrose were introduced—points to HFI (vs galactosemia, which reacts to milk).
2. Check urine reducing substances: will be positive in HFI (fructosuria) even though urine dipstick is negative for glucose.
3. If HFI is suspected, immediately remove all fructose sources from the diet (no further fruit, sucrose, sorbitol) and avoid any fructose-containing IV fluids or medications.
4. Confirm diagnosis with genetic testing for ALDOB gene mutations or an aldolase B enzyme assay (if available). Do not perform a fructose tolerance test (oral fructose challenge), as it can precipitate a dangerous reaction.
5. Differentiate from galactosemia: galactosemia presents in neonates fed milk (lactose/galactose) and often causes cataracts, whereas HFI presents after fruit/sugar introduction and does not cause cataracts.

1. Strict dietary elimination of fructose, sucrose, and sorbitol for life (no fruits, juices, table sugar, honey, syrups, etc.). Read ingredient labels carefully; even some medications/formulas contain fructose-based additives.
2. Ensure adequate nutrition: use alternative carbohydrate sources (glucose, starches) and supplement with a sugar-free multivitamin (to provide nutrients from fruits).
3. Manage acute episodes: if accidental fructose ingestion causes hypoglycemia or acidosis, give rapid IV glucose and correct metabolic disturbances (hydrate, bicarbonate if needed), while monitoring liver and kidney function.

• Mnemonic: FAB GUT – Fructose (Aldolase B deficiency) And Galactose (UridylTransferase deficiency) to remember the enzyme defects in HFI vs galactosemia.
• Aldolase B is Bad (life-threatening) while fructoKinase is OK: fructokinase deficiency (essential fructosuria) is harmless.

• Lethargy, vomiting, or seizure after feeding a baby fruits or sweets → think HFI until proven otherwise (emergency—check glucose, stop fructose immediately).
• Unexplained acute liver failure in an infant (especially after weaning onto foods) should prompt evaluation for inborn errors like HFI.

1. Fructose/sucrose exposure (e.g., juices, baby food) triggers symptoms in infant → suspect HFI.
2. If acute symptoms (seizures, etc.), stabilize (ABCs), give IV dextrose to reverse hypoglycemia, and eliminate any fructose sources right away.
3. Obtain labs: check blood glucose, electrolytes, liver enzymes, ABG/lactate (lactic acidosis), and do a urine reducing substance test (indicates fructose/galactose in urine).
4. Confirm HFI with genetic testing (biallelic ALDOB mutations) or enzyme assay on liver biopsy if needed; avoid any fructose challenge testing.
5. Long-term: Educate caregivers and implement a life-long fructose/sucrose/sorbitol-free diet; monitor growth and liver/renal function during follow-up.

• Previously healthy 6–8 month-old who begins fruit juices/purees, then develops vomiting, lethargy, seizures, and hepatomegaly after feeding → suspect hereditary fructose intolerance.
• Infant with hypoglycemic seizures after eating fruit, and urine positive for reducing sugars but negative on glucose dipstick → classic lab clue for HFI.