Fanconi-Bickel Syndrome ... (Fanconi-Bickel Syndrome) - Gen SLC2A2.
Fanconi syndrome-Bickel (FBS) is a disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired glucose utilization and galactose. This disease manifests itself in the first months of life with developmental delay, polyuria and losses related to the proximal tubules rickets. The protruding abdomen is the result of growth retardation and hepatosplenomegaly, being evident in early childhood. Puberty is delayed. In addition, it generalized osteopenia leading to fractures during childhood and described osteoporosis in later stages of life. Some patients also exhibit an abnormal distribution of fatty tissue. Other signs and symptoms include fasting hypoglycemia, ketonuria, diarrhea and hypercholesterolemia. It is believed to be related to a defect in the primary transport monosaccharides through the membranes, since there were observed enzyme defects in carbohydrate metabolism, being damaged the glucose and galactose.
This process is due to mutations in the SLC2A2 gene, located on the long arm of chromosome 3 (3q26.1-q26.2). This gene encodes a glucose transporter, which is expressed in hepatocytes, pancreatic and the basolateral wall of the intestinal epithelial cells and distal renal tubule beta cells. The encoded protein mediates bidirectional glucose transport through the plasma membrane of hepatocytes and is responsible for glucose uptake by beta cells. Because of their low affinity for glucose, it has been suggested as a glucose sensor. They may also be involved with the Na (+) / glucose cotransporter in transcellular transport of glucose in the small intestine and kidney.
They have identified more than 40 mutations in the SLC2A2 gene related Fanconi-Bickel syndrome (FBS). The identified mutations result in loss of functional glucose transporter, disrupting the transport of glucose and galactose. This leads to steatosis of the liver, as well as glycogen accumulation in hepatocytes and cells of the proximal renal tubules. Hyperglycemia can be explained by the decreased absorption of monosaccharides in the liver, which is enhanced by inappropriate secretion low insulin due to impaired glucose sensitive mechanism beta cells. Hypoglycemia during fasting can be explained by the transport of glucose altered outside the liver, which results in an increased level of intracellular glucose which in turn can inhibit the degradation of glycogen, leading to glycogen storage and hepatomegaly . Hypoglycemia is compounded by the loss of renal glucose due to faulty transport glucose and galactose through the basolateral membranes of tubule cells. Renal glycogen accumulation may occur as a consequence, resulting in the deterioration of other functions of tubule cells. The deterioration of the intestinal absorption of monosaccharides is not sufficient to prevent the increase in plasma glucose above the normal range. However, the altered transport of monosaccharides outside enterocytes may be responsible for the accumulation of glycogen putative enterocyte and, therefore, for diarrhea and malabsorption observed in some patients with FBS.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Fanconi-Bickel syndrome (FBS), by complete PCR amplification of exons SLC2A2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).