Fanconi-Bickel Syndrome (FBS)

At a glance

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. The association between a diabetes-like renal glomerular disease and the Fanconi-Bickel Syndrome must be confirmed.

Synonyms

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.

History

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

Incidence

Approximately 100 cases reported in the literature.

Genetic inheritance

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.

Pathophysiology

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.

Diagnosis

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.

Clinical aspects

Present in infancy (fever, vomiting, growth failure, and rickets). Later, affected individuals present 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 is based on symptomatic replacement treatment (water, ...