Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance

Are Heterozygous Carriers for Hereditary Fructose Intolerance Predisposed to Metabolic Disturbances When Exposed to Fructose?

Background: High fructose intake increases blood lactate, triglyceride and uric acid concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the general population. In patients with hereditary fructose intolerance fructose consumption is associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia.

Objective: We investigated whether asymptomatic carriers for hereditary fructose intolerance (HFI) would have a higher sensitivity to adverse effects of fructose than the general population.

Design: Eight subjects heterozygous for HFI (hHFI; 4 males, 4 females) and eight controls received for 7 days a low fructose diet and on the eighth day ingested a test meal calculated to provide 25% of basal energy requirement containing labeled fructose (13C fructose 0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg). Total fructose oxidation, total endogenous glucose production (by 6,6-2H2-glucose dilution), carbohydrate and lipid oxidation, lipids, uric acid, lactate, creatinine, urea and amino acids were monitored for 6 hours.

Inclusion Criteria:

• 8 healthy Volunteers (4 male, 4 female) parents of a child with hereditary fructose intolerance with ALDOB with heterozygous mutation of ALDOB gene
• 8 healthy Volunteers (4 male, 4 female), healthy with no mutation of ALDOB gene

Exclusion Criteria:

• Fasting glycemia > 7.0 mmol/L
• Fasting total triglycerides > 4.0 mmol/L
• Chronic renal insufficiency (eGFR ≤ 50 ml/min)
• Anemia (ferritin < 20 ug/L, hemoglobin < 13.5 ou 12.5 g/dl)
• Drugs
• Pregnancy