MUTATIONS IN GLUT2, THE GENE FOR THE LIVER-TYPE GLUCOSE-TRANSPORTER, IN PATIENTS WITH FANCONI-BICKEL-SYNDROME

Fanconi-Bickel syndrome (FBS) is a rare autosomal-recessive inborn err or of metabolism characterized by hepatorenal glycogen accumulation, F anconi nephropathy and impaired utilization of glucose and galactose(1 ), To date, no underlying enzymatic defect in carbohydrate metabolism has been identified. Therefore, and because of (he impairment of both glucose and galactose metabolism, a primary defect of monosaccharide t ransport across membranes has been suggested(1-4). Here we report muta tions in the gene encoding the facilitative glucose transporter 2 (GLU T2) in three FBS families, including the original patient described in 1949 by Fanconi and Bickel(5) Homozygous mutations were found in affe cted individuals, whereas all parents tested were heterozygous for the respective mutation. Because all detected mutations (Delta T446-449, C1251T and C1405T) predict truncated translation products that cannot be expected to have functional monosaccharide transport activity, GLUT 2 mutations are probably the cause of FBS.