Fanconi–Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene which codes for the glucose transporter protein 2 expressed in hepatocytes and renal tubular cells causing a defect in carbohydrate metabolism, hepatomegaly, severe hypophosphatemic rickets and failure to thrive.
Subjects and methods
Among 17 unrelated Egyptian families with heritable renal tubular acidosis, three families clinically suspected as FBS were enrolled for this study after providing written informed consent. The three families had positive consanguinity and index cases with characteristic clinical features of FBS (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy). Laboratory work-up included urinalysis, renal and liver function tests, fasting and postprandial blood sugar, serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile and arterial blood gas analysis. Imaging studies included bone survey and abdominal ultrasound. Liver biopsy was performed to confirm pathological diagnosis of the liver enlargement. Molecular analysis was performed for all family members—polymerase chain reaction followed by direct sequencing of the coding segments as well as the flanking introns.
Three different mutations were detected, one specific for each family, including two new mutations. In the first family, exon 3, two bases (GA) were deleted (c.253_254delGA causing a frameshift mutation (p. Glu85fs); the patient presented with early symptoms but unfortunately died despite adequate treatment. In the second family, a mutation was found in exon 6, in the splicing acceptor site with intron 5 (c.776-1G>C or IVS5-1G>A). The third family showed a missense mutation C-to-T substitution at c.1250 (c.1250C>T) causing change of codon 417 (CCG) for proline to CTG for leucine (p. P417L); this is a well-known mutation in the Arab population previously localized in exon 9; however, it is currently renumbered to exon 10.
Neither the new mutations nor the reported one were particularly more frequent; however, the third mutation (c.1250C>T) needs more attention in survey studies especially if performed in Arab patients as it has been renumbered because of the ‘change’ of gene structure since the initial reports.
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Santer R, Schneppenheim R, Suter D, Schaub J, Steinmann B. Fanconi–Bickel syndrome—the original patient and his natural history, historical steps leading to the primary defect, and a review of the literature. Eur J Pediatr. 1998;157:783–97.
Santer R, Steinmann B, Schaub J. Fanconi–Bickel syndrome—a congenital defect of facilitative glucose transport. Curr Mol Med. 2002;2:213–27.
Sakamoto O, Ogawa E, Ohura T, Igarashi Y, Matsubara Y, Narisawa K, et al. Mutation analysis of the GLUT2 gene in patients with Fanconi–Bickel syndrome. Pediatr Res. 2000;48:586–9.
Gopalakrishnan A, Kumar M, Krishnamurthy S, Sakamoto O, Srinivasan S. Fanconi–Bickel syndrome in a 3-year-old Indian boy with a novel mutation in the GLUT2 gene. Clin Exp Nephrol. 2011;15:745–8.
Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi–Bickel syndrome. Nat Genet. 1997;17:324–6.
Santer R, Groth S, Kinner M, Dombrowski A, Berry GT, Brodehl J, et al. The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi–Bickel syndrome. Hum Genet. 2002;110:21–9.
Temizel IN, Coskun T, Yüce A, Kocak N. Fanconi–Bickel syndrome in three Turkish patients with different homozygous mutations. Turk J Pediatr. 2005;47:167–9.
Ozer EA, Aksu N, Uclar E, Erdogan H, Bakiler AR, Tsuda M, et al. No mutation in the SCL2A2 (GLUT2) gene in a Turkish infant with Fanconi–Bickel syndrome. Pediatr Nephrol. 2003;18:397–8.
Şimşek E, Savaş-Erdeve S, Sakamoto O, Doğancı T, Dallar Y. A novel mutation of the GLUT2 gene in a Turkish patient with Fanconi–Bickel syndrome. Turk J Pediatr. 2009;51:166–8.
Burwinkel B, Sanjad SA, Al-Sabban E, Al-Abbad A, Kilimann MW. A mutation in GLUT2, not in phosphorylase kinase subunits, in hepato-renal glycogenosis with Fanconi syndrome and low phosphorylase kinase activity. Hum Genet. 1999;105:240–3.
Takeda J, Kayano T, Fukomoto H, Bell GI. Organization of the human GLUT2 (pancreatic beta-cell and hepatocyte) glucose transporter gene. Diabetes. 1993;42(5):773–7.
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Al-Haggar, M., Sakamoto, O., Shaltout, A. et al. Mutation analysis of the GLUT2 gene in three unrelated Egyptian families with Fanconi–Bickel syndrome: revisited gene atlas for renumbering. Clin Exp Nephrol 16, 604–610 (2012). https://doi.org/10.1007/s10157-012-0603-9
- Fanconi–Bickel syndrome (FBS)
- Glycogen storage (GSD XI)
- GLUT2 or SLC2A2 gene