Fanconi-Bickel syndrome (FBS) is a rare autosomal-recessive inborn error of metabolism characterized by hepatorenal glycogen accumulation, Fanconi nephropathy and impaired utilization of glucose and galactose. To date, no underlying enzymatic defect in carbohydrate metabolism has been identified. Therefore, and because of the impairment of both glucose and galactose metabolism, a primary defect of monosaccharide transport across membranes has been suggested. Here we report mutations in the gene encoding the facilitative glucose transporter 2 (GLUT2) in three FBS families, including the original patient described in 1949 by Fanconi and Bickel. Homozygous mutations were found in affected 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, GLUT2 mutations are probably the cause of FBS.
