Molecular Diagnosis of Hereditary Fructose Intolerance

Abstract

To the Editor.—— The recent article by Burmeister et al1demonstrated the use of the intravenous fructose tolerance test in establishing the diagnosis of hereditary fructose intolerance (HFI). However, the administration of fructose, deliberately or inadvertently, to such patients is not without hazard (as in the reported case) and on more than one occasion has proven fatal.2,3A less hazardous diagnostic test for HFI would, therefore, be welcome. Recent advances in understanding the molecular pathogenesis of HFI offer the possibility of diagnosis by direct molecular analysis of human genes. Hereditary fructose intolerance is transmitted in an autosomal recessive manner and results from a deficiency of the enzyme aldolase B that normally cleaves fructose-1-phosphate. Characterization of the gene for aldolase B, which is located on chromosome 9, has shown two common missense point mutations in HFI (designated A149P and A174D) that result in catalytic deficiency of aldolase B. Most