The fanconi syndrome associated with hepatic glycogenosis and abnormal metabolism of galactose

Fanconi-Bickel syndrome - the original patient and his natural history, historical steps leading to the primary defect, and a review of the literature

“…Consanguinity in families also suggested autosomal recessive inheritance of FBS. This type of inheritance was further supported by the occurrence of FBS in siblings (Families 14,21,24,30,45,47,48,64,65), and the proximity of places of residence of patients (Cases 2 and 13, 10 and 30). It was ®nally proven by the detection of homozygous mutations in the Glut2 gene in a high proportion of FBS patients (64%), with compound heterozygozity being responsible for the remainder (Santer et al, submitted).…”

“…The role of both mechanisms has not been suciently studied in FBS. An inappropriate insulin response on intravenous glucose loading has been documented in a few cases [21,30,50]. Also hypoglycaemia during fasting may be explained by two mechanisms: (1) an 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, and (2) exacerbation of hypoglycaemia by renal loss of glucose due to a transport defect for glucose and galactose across the basolateral membranes of the proximal tubular cells.…”

SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion

“…We consider that the neonatal diabetes found in patients with recessive inactivating SLC2A2 mutations is likely to reflect impaired insulin secretion given: (1) the response to insulin therapy in doses similar to other subtypes of neonatal diabetes; (2) the relatively low C-peptide levels at glucose values >20 mmol/l measured at diagnosis in two of our patients; (3) the inappropriately low insulin secretion associated with glucose intolerance reported in many FBS patients [8,[12][13][14][15]; and (4) the low birthweight seen in all patients, similar to other causes of neonatal diabetes, and consistent with reduced fetal insulin secretion in utero. We could not find data to assess if birthweight was reduced in FBS patients who are not diagnosed with neonatal diabetes.…”

GLUT2, glucose sensing and glucose homeostasis

“…Impaired GSIS in adult Fanconi-Bickel patients have only been reported in a few cases [84][85][86], but inactivating mutations in GLUT2 have been found to cause transient neonatal diabetes mellitus [87]. As this condition disappears after approximately 18 months, this indicates that there is a transient requirement for GLUT2 for the control of insulin secretion in the first months of life.…”