HEREDITARY FRUCTOSE INTOLERANCE

Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1. 2.13), is a recessively inherited condition in which affected homozygo tes develop hypoglycaemic and severe abdominal symptoms after taking f oods containing fructose and cognate sugars. Continued ingestion of no xious sugars leads to hepatic and renal injury and growth retardation; parenteral administration of fructose or sorbitol may be fatal. Direc t detection of a few mutations in the human aldolase B gene on chromos ome 9q facilitates the genetic diagnosis of HFI in many symptomatic pa tients. The severity of the disease phenotype appears to be independen t of the nature of the aldolase B gene mutations so far identified. It appears that hitherto there has been little, if any, selection agains t mutant aldolase B alleles in the population: in the UK, similar to 1 .3% of neonates harbour one copy of the prevalent A149P disease allele . The ascendance of sugar as a major dietary nutrient, especially in w estern societies, may account for the increasing recognition of HFI as a nutritional disease and has shown the prevalence of mutant aldolase B genes in the general population. The severity of clinical expressio n correlates well with the immediate nutritional environment, age, cul ture, and eating habits of affected subjects. Here we review the bioch emical, genetic, and molecular basis of human aldolase B deficiency in HFI, a disorder which responds to dietary therapy and in which the pr incipal manifestations of disease are thus preventable.