Abstract
Accumulation of glycogen in the kidney and liver is the main feature of Fanconi–Bickel Syndrome (FBS), a rare disorder of carbohydrate metabolism inherited in an autosomal recessive manner due to SLC2A2 gene mutations. Missense, nonsense, frame-shift (fs), in-frame indels, splice site, and compound heterozygous variants have all been identified in SLC2A2 gene of FBS cases. Approximately 144 FBS cases with 70 different SLC2A2 gene variants have been reported so far. SLC2A2 encodes for glucose transporter 2 (GLUT2) a low affinity facilitative transporter of glucose mainly expressed in tissues playing important roles in glucose homeostasis, such as renal tubular cells, enterocytes, pancreatic β-cells, hepatocytes and discrete regions of the brain. Dysfunctional mutations and decreased GLUT2 expression leads to dysglycaemia (fasting hypoglycemia, postprandial hyperglycemia, glucose intolerance, and rarely diabetes mellitus), hepatomegaly, galactose intolerance, rickets, and poor growth. The molecular mechanisms of dysglycaemia in FBS are still not clearly understood. In this review, we discuss the physiological roles of GLUT2 and the pathophysiology of mutants, highlight all of the previously reported SLC2A2 mutations associated with dysglycaemia, and review the potential molecular mechanisms leading to dysglycaemia and diabetes mellitus in FBS patients.
Highlights
Fanconi–Bickel syndrome (OMIM# 227810), a carbohydrate metabolism disorder due to glucose transporter 2 (GLUT2) transporter defect was first described by Fanconi and Bickel in 1949 [1]
We briefly summarize the role of GLUT2 in glucose physiology, review all the reported mutations in SLC2A2, which have been reported with dysglycaemia and we discuss the potential molecular mechanisms of dysglycaemia associated with Fanconi–Bickel Syndrome (FBS)
A large number of the reported patients with FBS have dysglycaemia characterized by post-prandial hyperglycemia, fasting hypoglycemia, glucose intolerance, and rarely diabetes mellitus
Summary
Fanconi–Bickel syndrome (OMIM# 227810), a carbohydrate metabolism disorder due to glucose transporter 2 (GLUT2) transporter defect was first described by Fanconi and Bickel in 1949 [1]. In 1987, Fanconi–Bickel Syndrome (FBS) was identified as a defect in a sodium glucose secondary active transporter responsible for galactose and glucose transport in many tissues, including kidney and liver [2]. In 1994, a study in Xenopus oocytes proved that a highly conserved GLUT2 missense mutation in one allele of the gene (substituted Val197 to Ile197) leads to GLUT2 dysfunction, and might be expected to play an important role in pathogenicity of non-insulin dependent diabetes mellitus [4,5]. In 1997, Santer et al (1997) for first time described the role of GLUT2 (SLC2A2) gene mutations in three FBS affected families, that includes the original patient reported by Fanconi and Bickel in 1949 [6]. We briefly summarize the role of GLUT2 in glucose physiology, review all the reported mutations in SLC2A2, which have been reported with dysglycaemia and we discuss the potential molecular mechanisms of dysglycaemia associated with FBS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
