Hereditary fructose intolerance

Hereditary fructose intolerance (HFI), also known as fructose-1,6-bisphosphate aldolase B deficiency or aldolase B deficiency, is a rare inherited metabolic disorder caused by a deficiency of the enzyme aldolase B (fructose-1,6-bisphosphate aldolase) in the liver, kidneys, and small intestine. This enzyme is essential for the metabolism of fructose. When individuals with HFI ingest fructose, sucrose (table sugar), or sorbitol, the accumulation of fructose-1-phosphate in these organs leads to toxic effects including severe hypoglycemia, nausea, vomiting, abdominal pain, and bloating. The disease is caused by pathogenic variants in the ALDOB gene located on chromosome 9q31.1. Symptoms typically first appear in infancy when fructose-containing foods (such as fruits, juices, or sweetened formulas) are introduced into the diet. Acute episodes following fructose ingestion can cause sweating, trembling, confusion, and lethargy due to profound hypoglycemia. Chronic or repeated exposure to fructose can lead to progressive liver damage (hepatomegaly, jaundice, cirrhosis), renal tubular dysfunction (proximal renal tubular acidosis), failure to thrive, and potentially life-threatening liver and kidney failure. Coagulopathy and lactic acidosis may also occur during acute episodes. The cornerstone of treatment is strict lifelong dietary avoidance of fructose, sucrose, and sorbitol. When the diagnosis is made early and the diet is adhered to rigorously, individuals with HFI can lead normal, healthy lives with an excellent prognosis. Many affected individuals develop a natural aversion to sweet foods. Diagnosis is confirmed through molecular genetic testing of the ALDOB gene or, less commonly, by enzymatic assay of liver biopsy tissue. Intravenous glucose administration is the emergency treatment for acute hypoglycemic episodes. Patients should also be cautious about medications and intravenous solutions that may contain fructose, sucrose, or sorbitol as excipients.

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