Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant

J Pediatr Endocrinol Metab. 2019 Nov 26;32(11):1229-1233. doi: 10.1515/jpem-2019-0235.


Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2) protein. The clinical manifestations include hepatomegaly, conditional hypo/hyperglycemia, rickets, short stature and proximal renal tubular dysfunction. GLUT2 regulates monosaccharide homeostasis through sugar sensing and transmembrane transportation during high/low glucose levels. In the current study, we present two siblings suffering from FBS. The patients presented with doll-like facies, failure to gain weight and height, abdominal distension and firm hepatomegaly. The family had a history of deaths of twin male siblings in the neonatal period and twin female siblings at ages 10 months and 2.5 years, respectively. Clinical presentation and biochemical investigations including a complete blood count, electrolytes, liver and renal function tests suggested FBS. Mutation screening of SLC2A2 confirmed the diagnosis with identification of a novel homozygous splice site variant predicting an in-frame deletion [p.(Gly166-S169del)] in the GLUT2 protein. The in-silico analysis predicted the variant to affect the three-dimensional conformation of the fourth transmembrane helix of the encoded protein, rendering the non-functionality of GLUT2 in both patients of the family under study.

Keywords: Fanconi-Bickel syndrome; GLUT2; GTR2; SLC2A2; glycogen storage disease (GSD) type XI.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • DNA Mutational Analysis
  • Fanconi Syndrome / genetics*
  • Fanconi Syndrome / pathology*
  • Female
  • Genes, Recessive
  • Genetic Testing / methods*
  • Glucose Transporter Type 2 / genetics*
  • Humans
  • Infant
  • Mutation*
  • Pakistan
  • Phenotype
  • Prognosis
  • RNA Splicing*
  • Sequence Deletion


  • Glucose Transporter Type 2
  • SLC2A2 protein, human