Fanconi–Bickel syndrome – A congenital defect of the liver-type facilitative glucose transporter

1 Department Pediatricsof of Childrenˇs, University Kiel; 2 Municipal Hospital,Esslingen, Germany; 3 Division of Metabolic and Molecular Diseases, Department ofPediatrics, University Zurichof , Switzerland* Correspondence: University Childrenˇs Hospital, Schwanenweg 20, D-24105 Kiel,GermanyIn 1949, Fanconi and Bickel reported the —rst patient with a rare autosomal reces-sive inborn error of metabolism characterized by hepatorenal glycogen accumula-tion, fasting hypoglycaemia, postprandial hyperglycaemia and hypergalactosaemia,and a Fanconi-type nephropathy with disproportionately severe glucosuria(Fanconi 1949).and Bickel To date, approximately 30 cases of this condition havebeen reported; it has been termed Fanconi¨Bickel syndrome (FBS) et al(Manz1987) (Hug 1987).or glycogen storage disease type XI The latter classi—cation wasbased on the assumption that an enzymatic defect of phosphoglucomutase was theunderlying cause. Recently, however, we were able to show that a congenital defectof the liver-type glucose transporter Glut2 is the basic defect et al(Santer 1997).Here we present a model that shows that a Glut2 defect explains most of the patho-physiological events encountered in this condition.PATIENTS AND METHODSFour patients with characteristic clinical and biochemical features of FBS (includingthe original patient described by Fanconi and Bickel) from 3 families were investi-gated. A mutation screening covering the complete coding sequence of the Glut2gene was performed by polyacrylamide gel electrophoresis of single- and double-stranded PCR products, direct sequencing of samples showing an aberrant patternand conformation of detected mutations by restriction enzyme digest.RESULTS AND DISCUSSIONIn all aƒected individuals a homozygous mutation (*T446¨449, C1213T or C1405T)in the Glut2 gene could be detected. All mutations predict a premature terminationof translation and a loss of glucose transport activity et al(Santer 1997).191