Abstract

Objective: Hereditary fructose intolerance (HFI; OMIM 229600) is an autosomal recessive inborn error of metabolism with an estimated prevalence of 1 in 10,000 worldwide. Patients exhibit metabolic disturbances and experience typical symptoms once fructose-containing foods are first introduced into the diet. Affected children may develop an aversion to fructose-containing foods, and these feeding habits can partially protect them, often resulting in HFI remaining undiagnosed until adulthood.

Patients and Methods: We conducted a retrospective observational analysis of a cohort of 14 adult patients with HFI referred to the Adult Metabolic Disease Clinic at Careggi University Hospital (Florence, Italy).

Results: Eight patients were diagnosed in adulthood. The most frequent mutations in the ALDOB gene were p.Ala150Pro and p.Ala175Asp, consistent with previous literature. Gastrointestinal symptoms and symptomatic hypoglycemia were the most common clinical manifestations. All patients had an aversion to sweet foods and fruit since early childhood, and their nutritional history was a key to the diagnosis. Hepatomegaly was the most important clinical feature, present both at diagnosis and at last follow-up. In six cases, other diagnoses were initially made, including eating disorders, epilepsy, chronic intestinal diseases, and glucose intolerance. At the last clinical evaluation, patients had a normal weight, and liver enzymes, creatinine, fasting plasma glucose, and lipid profiles were within the normal ranges. Two patients had osteoporosis/osteopenia, and only one developed a vitamin B12 deficiency.

Conclusions: HFI is an inborn error of metabolism with varying severity of clinical manifestations. The diagnosis requires careful history-taking, particularly focusing on nutritional habits, and is confirmed by molecular analysis of the ALDOB gene. A lifelong fructose-free diet prevents complications, but chronic morbidity can still develop. Patients require periodic clinical and metabolic monitoring to assess dietary adherence, general health, and possible diet-related nutritional deficiencies.