Fanconi-Bickel Syndrome (FBS)

Genetically transmitted metabolic disorder of carbohydrates characterized by accumulation of glycogen in the liver with hepatomegaly, proximal tubular nephropathy, fasting hypoglycemia, glucose (and galactose) intolerance, and dwarfism.

Hepatorenal Glycogenosis with Renal Fanconi Syndrome; Hepatic Glycogenosis with Fanconi Nephropathy; Hepatic Glycogenosis with Aminoaciduria and Glucosuria; Fanconi Syndrome with Intestinal Malabsorption and Galactose Intolerance; Pseudo-Phlorizin Diabetes; Glycogenosis, Fanconi type; Glycogen Storage Disease IX; Bickel-Fanconi Syndrome.

Inborn error of carbohydrate metabolism with tubular nephropathy. First reported in 1949 by Guido Fanconi, a Swiss pediatrician, and Horst Bickel, a German physician.

Approximately 100 cases reported in the literature.

Autosomal recessive inheritance. Caused by mutations in the glucose transporter protein 2 (GLUT2 gene) that is expressed in liver, pancreas, intestine, and kidney. Gene map locus is 3q26.1-q26.3.

Primary defect of monosaccharide transport across the membranes. Hyperglycemia (and hypergalactosemia) in the fed state could be explained by (1) a decreased monosaccharide uptake by the liver or (2) an inappropriately low insulin secretion caused by impairment of the glucose-sensing mechanism of the beta cells. Hypoglycemia during fasting may result from (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, or (2) exacerbation of hypoglycemia due to an increased renal loss of glucose caused by a transport defect for glucose and galactose across the basolateral membranes of the proximal tubular cells. As a consequence, renal glycogen accumulation may occur, with impairment of other functions of the proximal tubular cells and the characteristic clinical picture of Fanconi nephropathy with disproportionately severe glucosuria. As a consequence of a transport defect for glucose and galactose at the basolateral membrane, intestinal monosaccharide transport also is affected, resulting in malabsorption and diarrhea.

Characterized by hepatomegaly. It is caused by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose. Glucosuria is considered a most prominent finding.

Present in infancy (fever, vomiting, growth failure, and rickets). Later patients present with dwarfism, protuberant abdomen, hepatomegaly, moon-shaped face, and fat deposition about the shoulders and abdomen. Emergence of the teeth and development of puberty are retarded. Fractures and pancreatitis are complications. Rickets and osteoporosis later in life are constant features. Glomerular filtration rate is normal or low normal, and there is no progression to glomerular insufficiency or deterioration of tubular defects. Polyuria, probably a result of osmotic diuresis, is a constant finding. Clinical management by symptomatic replacement treatment (water, electrolytes, and vitamin D, restriction of galactose, a diabetes mellitus-like diet presented in frequent small meals with adequate caloric intake). Administration of uncooked cornstarch has been reported to be beneficial for promoting growth. Few patients reported still alive in their 50s.

Preoperative fasting should be kept as brief as possible and intravenous glucose started to minimize the possibility of hypoglycemia. Frequent measurement of blood glucose concentrations is mandatory. Detailed assessment of hepatic functions in view of glycogen accumulation. Blood work should include serum concentrations of urea, creatinine, and electrolytes and liver function tests.

Anesthetic management depends on the severity of the disease. Intraoperative hypoglycemia may be difficult to recognize because the signs and symptoms are masked by general anesthesia. Consequently, regular blood glucose level monitoring is mandatory. Adequate intravascular fluid replacement in the presence of osmotic diuresis. Sympathetic blockade induced by spinal or epidural anesthesia may abolish any homeostatic adrenergic responses to hypoglycemia.

Sedative premedications are not recommended because they may mask hypoglycemic symptoms. Similarly, postoperative analgesia and sedation must be administered in guarded doses. Avoid any drug that is a potential threat to hepatocellular integrity. Sevoflurane is not associated with an increased risk of renal toxicity when compared with other commonly used volatile anesthetics. However, prolonged low-flow administration of sevoflurane must be done with caution because of the significant increase in compound A. Avoid nephrotoxic agents. Avoid drugs that are dependent upon the liver or kidneys for metabolism and elimination (e.g., gallamine, pancuronium).