Hereditary fructose intolerance

Hereditary fructose intolerance (HFI) is an inborn error of carbohydrate metabolism that is inherited as an autosomal recessive condition. The disease is caused by a catalytic deficiency of aldolase B and is characterized by severe abdominal symptoms and hypoglycaemia which follow the ingestion of fructose, sucrose or sorbitol. The exact prevalence of HFI in different populations is unknown but studies from Switzerland suggest a disease frequency of about 1 in 20,000 live births, thus predicting a carrier frequency of greater than 1% and a gene prevalence that approaches polymorphic frequency. It is notable that many patients who endure severe symptoms during early infancy develop a marked aversion to harmful foodstuffs and thereby survive to adulthood. Although exposure to fructose may prove to be fatal in this disorder, institution of a strict exclusion diet is curative. HFI, when treated rigorously after diagnosis, is thus compatible with a long and healthy life. HFI vividly illustrates the interplay of dietary factors and heredity in the development of human disease. The recent identification of genetic lesions that cause this disorder further demonstrates the remarkable clinical benefits that may accrue from the study of the molecular basis of inherited diseases and its population genetics: it is now possible to detect asymptomatic disease carriers and diagnose the disorder in affected families by non-invasive analysis of small samples of genomic DNA. Moreover, the systematic investigation of natural mutations in the human gene for aldolase B has allowed regions that are critical for catalytic function of this enzyme to be identified as part of an extended study of its molecular biology.