Santer et al. (1997) noted that a functional loss of GLUT2 is compatible with the clinical symptoms observed in subjects with FBS. Hyperglycemia (and hypergalactosemia) in the fed state can be explained by decreased monosaccharide uptake by the liver. Santer et al. (1997) stated that hyperglycemia in FBS is enhanced by an inappropriately low insulin secretion due to impairment of the glucose-sensing mechanism of the beta-cells. Data on insulin levels in FBS are limited; however, Manz et al. (1987) reported that intravenous glucose loading failed to raise serum insulin levels in one patient examined. Santer et al. (1997) postulated that hypoglycemia during fasting may be explained by altered glucose transport out of the liver, resulting in an increased intracellular glucose level that in turn may inhibit glycogen degradation, leading to glycogen storage and hepatomegaly. Hypoglycemia is exacerbated by renal loss of glucose due to a transport defect for glucose and galactose across the basolateral membranes of the tubular cells. Santer et al. (1997) suggested that renal glycogen accumulation may occur as a consequence, resulting in the impairment of other functions of the tubular cells and the characteristic clinical picture of Fanconi nephropathy with disproportionately severe glucosuria. The impairment of intestinal monosaccharide absorption is not sufficient to prevent the increase of plasma glucose above the normal range (Aperia et al., 1981); however, the altered transport of monosaccharides out of the enterocytes may be responsible for putative enterocyte glycogen accumulation and, as a consequence, for diarrhea and malabsorption observed in some patients with FBS (Santer et al., 1997).
