title: Elements of diabetic nephropathy in a patient with GLUT 2 deficiency.
abstract: The Fanconi-Bickel syndrome is caused by homozygosity or compound heterozygosity for mutations of the facilitated glucose transporter 2 gene (GLUT2). Glycogen accumulates in renal tubular cells and they fail to reabsorb multiple filtered solutes because of impairment in GLUT2-mediated efflux of glucose. We describe a 10-year-old male child with GLUT2 deficiency who produced massive amounts of 3-deoxyfructose (3-DF) in the kidneys. Since 3-DF is a detoxification product of a potent glycating agent, 3-deoxyglucosone, a precursor of advanced glycation end-products, this suggests a massive accumulation of glucose within tubular cells probably as a consequence of GLUT2 deficiency. The level of 3-DF in the urine of this atypical patient, who also manifested renal glomerular hyperfiltration, microalbuminuria, and glomerular mesangial expansion, was higher than in any patient examined with diabetes mellitus. Elevated levels of glucose and/or its metabolites in renal tubular cells may be necessary but not sufficient for the development of both the renal tubulopathy and diabetic-like glomerular disease in GLUT2 deficiency.
authors.affiliation: Department of Pediatrics, Divisions of Human Genetics and Molecular Biology and Endocrinology and Diabetes, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. gerard.berry@jefferson.edu
authors.forename: Gerard T
authors.initials: GT
authors.lastname: Berry
authors.forename: John W
authors.initials: JW
authors.lastname: Baynes
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wells-Knecht
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Szwergold
authors.forename: René
authors.initials: R
authors.lastname: Santer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D005198:Fanconi Syndrome / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007661:Ketoses / Q000652:urine; D008297:Male; D008875:Middle Aged
chemical_list: D051273:Glucose Transporter Type 2; D007661:Ketoses; C495680:SLC2A2 protein, human; C068286:3-deoxyhexulose