Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by the combination of hepatorenal glycogen accumulation and Fanconi-type nephropathy. Mutations in GLUT2, the gene for facilitative glucose transporter protein 2 (GLUT2), cause FBS. Aim: To evaluate glucose and Insulin responses to oral glucose load in patients with FBS. Methods: Ten children (7.3 ± 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbA_1c, insulin-like growth factor-I, and fasting lipid profiles were also measured. Results: Mean fasting and 2-h PG concentrations were 3.8 ± 0.9 mmol/l and 8.6 ± 3.0 mmol/l, respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and between 7.75 and 11.1 mmol/l in four patients (40%). HbA_1c, was normal in all the patients with a mean of 5.4 ± 0.3%. Mean fasting and peak serum insulin levels were 8.7 ± 0.8 pmol/l and 98.6 ± 43.0 pmol/l, respectively, and did not differ between the patients with normal and abnormal OGTT. Patients with abnormal OGTT were younger (4.8 ± 3.2 vs 11.0 ± 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p <0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated. Conclusions: Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbA_tc. Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.