Original Investigation

Human Genetics

, Volume 110, Issue 1, pp 21-29

First online:

The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome

  • René SanterAffiliated withDepartment of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany Email author 
  • , Sebastian GrothAffiliated withDepartment of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany
  • , Martina KinnerAffiliated withDepartment of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany
  • , Anja DombrowskiAffiliated withDepartment of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany
  • , Gerard T. BerryAffiliated withDivision of Endocrinology and Diabetes, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pa., USA
  • , Johannes BrodehlAffiliated withDepartment of Pediatrics, Medical School Hannover, Hannover, Germany
  • , James V. LeonardAffiliated withGreat Ormond Street Hospital for Children and Institute of Child Health, University College London, London, UK
  • , Shimon MosesAffiliated withDepartment of Pediatrics, Soroka University Medical Center, Beer Sheva, Israel
  • , Svante NorgrenAffiliated withDepartment of Pediatrics, Huddinge University Hospital and Karolinska Institute, Stockholm, Sweden
    • , Flemming SkovbyAffiliated withDepartment of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark
    • , Reinhard SchneppenheimAffiliated withDepartment of Pediatric Hematology and Oncology, University Children's Hospital, Hamburg, Germany
    • , Beat SteinmannAffiliated withDepartment of Pediatrics, University Children's Hospital, Zurich, Switzerland
    • , Jürgen SchaubAffiliated withDepartment of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany

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Abstract.

We report a total of 23 novel mutations of the SLC2A2 (GLUT2) gene in 49 patients with a clinical diagnosis of Fanconi-Bickel syndrome (FBS). Molecular genetic analysis has now been performed in more than 50% of the 109 FBS cases from 88 families that we have been able to locate world-wide since the original report in 1949. In these 49 patients, 33 different SLC2A2 mutations (9 missense, 7 nonsense, 10 frameshift, 7 splice-site) have been detected. Thus, our results confirm that mutations of SLC2A2 are the basic defect in patients with FBS. Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time. Mutations were also found in patients with atypical clinical signs such as intestinal malabsorption, failure to thrive, the absence of hepatomegaly, or renal hyperfiltration. No single prevalent SLC2A2 mutation was responsible for a significant number of cases. In a high percentage (74%) of FBS patients, the mutation is homozygous, so we conclude that the prevalence of SLC2A2 mutations is relatively low in most populations. No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected.