MOLECULAR BIOLOGICAL INVESTIGATION IN A F AMILY WITH HEREDITARY FRUCTOSE INTOLERANCE AND DIAGNOSTIC CONSEQUENCES

Background: Advances in molecular diagnostics give rise to a reconside ration of the diagnostic strategy in hereditary fructose intolerance, In a family with hereditary fructose intolerance and a well documented index patient the diagnostic procedure is demonstrated with a male br east-fed infant. Methods: The detection of the most common point mutat ion A149P in the aldolase B gene of this family was performed by ampli fication of exon V and cleavage of the PCR product with the restrictio n endonuclease AhaII. In addition, the defect in exon V was demonstrat ed by SSCP (single strand conformational polymorphism) analysis. Resul ts: By means of these methods, the homozygotic occurrence of this muta tion in the patient could be proved. Additional diagnostic arrangement s were abandoned. To our knowledge is this the very first example that a patient with hereditary fructose intolerance was reliably diagnosed although he was fed fructose free and had never shown any signs of a metabolic disturbances. Conclusions: Therefore, we propose, that when a hereditary fructose intolerance is suspected from the nutritional hi story and the clinical picture, at first molecular biological methods should be used for the search for mutations in the aldolase B gene, In vasive procedures such as fructose tolerance test or liver biopsy shou ld be applied only if the molecular biological approach has failed.