Genotypic and Phenotypic Characteristics of Turkish Patients with Hereditary Fructose Intolerance

Introduction: Hereditary fructose intolerance (HFI) is an autosomal recessive inherited metabolic disorder characterized by a deficiency of the fructose-1-phosphate aldolase (aldolase B) enzyme, caused by biallelic pathogenic variants in the ALDOB gene on chromosome 9q31.1. Methods: We retrospectively analyzed the demographic, clinical, biochemical, and molecular genetic characteristics of nine patients from eight unrelated Turkish families diagnosed with HFI over the past ten years at a single center. Results: Patients with HFI showed an aversion to sugar-containing foods and generally had a favorable prognosis. The most common presenting complaints or reasons for referral to our clinic in this cohort were vomiting, hepatosteatosis, and elevated transaminases. Fructose aversion was present in all patients, representing a protective adaptive behavior rather than a complaint, and was therefore not reported as a symptom. Hypoglycemic syncope was observed in only one patient, while no significant hypoglycemia or metabolic acidosis was detected in the others. Urinary reducing substances and urine sugar chromatography were negative, likely due to the avoidance of fructose-containing foods. The p.Ala150Pro, and p.Ala175Asp were identified as the most frequent variants. Homozygous variants (87.5%) were more common than compound heterozygous variants (12.5%). Conclusion: Genetic analysis of the ALDOB gene should be performed in patients with clinically suspected HFI to confirm the diagnosis. The p.Ala150Pro and p.Ala175Asp variants were the most frequent, consistent with previous reports in Turkish patients and individuals of European ancestry.