Objectives: Hereditary fructose intolerance is caused by a deficiency of the aldolase B enzyme, which is expressed in the liver, small intestine and kidneys. Patients usually show a marked aversion to fruits and sweets; if, however, it is not diagnosed, persistent or incidental ingestion of fructose might be lethal. Our paper aims at improving the clinical and molecular characterizations of these patients, to avoid dangerous misdiagnoses.
Methods: Here we report the molecular results in an Italian cohort: on the occurrence of aldolase B mutations and, in particular, on the clinical and molecular characterization of a large family with recurrent hereditary fructose intolerance.
Results: Patients included in our cohort showed the three most common mutations (p.A150P, p.A175D and p.N335K). Such molecular tests were enough to cover all the mutated alleles of hereditary fructose intolerance found in our patients. The allele frequencies of hereditary fructose intolerance mutations detected were 69.2% for p.A150P, 23.1% for p.A175D and 7.7% for p.N335K. The proband of the family with recurrence of the disease was heterozygous for the known p.A150P and p.A175D mutated alleles of the aldolase B gene. Molecular characterization of at-risk family members also identified the p.N335K mutation. In addition, the oldest affected patients exhibited mild clinical impairment.
Conclusions: Our results indicate that the diagnosis of hereditary fructose intolerance can be complicated by clinical and genetic intrafamilial variability. A knowledge of the clinical and geographical history of each family member is thus essential, to reduce potentially lethal misdiagnoses and to facilitate such patients to receive appropriate genetic counselling.