Disease relevance of Fanconi Syndrome

• Tcf1-/- mice have type 2 diabetes, dwarfism, renal Fanconi syndrome, hepatic dysfunction and hypercholestrolemia [1].
• Two postrenal transplant subjects with cystinosis but without Fanconi syndrome also had normal plasma carnitine levels [2].
• The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome [3].
• Four subjects with Fanconi syndrome but not cystinosis displayed the same abnormal pattern of plasma carnitine levels; controls with acidosis or a lysosomal storage disorder (Fabry disease), but not Fanconi syndrome, had entirely normal plasma carnitine levels [2].
• The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder characterized by severe mental retardation, congenital cataracts and renal Fanconi syndrome [4].

High impact information on Fanconi Syndrome

• Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered [5].
• Plasma and urine free and acyl carnitine were measured in 19 children with nephropathic cystinosis and renal Fanconi syndrome [2].
• In renal Fanconi syndrome, failure to reabsorb free and acyl carnitine results in a secondary plasma and muscle free carnitine deficiency [2].
• Two cystinotic patients fasted for 24 h and one idiopathic Fanconi syndrome patient fasted for 5 h showed normal increases in plasma beta-hydroxybutyrate and acetoacetate, which suggested that hepatic fatty acid oxidation was intact despite very low plasma free carnitine levels [2].
• Ifosfamide-induced Fanconi syndrome [6].

Chemical compound and disease context of Fanconi Syndrome

• Total free carnitine excretion in Fanconi syndrome patients correlated with total amino acid excretion (r = 0.76) [2].
• The data suggest that, in this model of Fanconi syndrome, the defective renal reabsorption of proline and glucose is associated with an alteration of luminal transport system [7].
• From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase) [8].
• Fanconi syndrome associated with didanosine therapy [9].
• Treatment with oral pancreatic and parenteral vitamin D supplements led to full recovery of the rachitic syndrome and the proximal renal tubular dysfunction [10].

Biological context of Fanconi Syndrome

• Other disorders occur due to loss of affinity or capacity of the cellular active transport systems for specific solutes, such as amino acids (renal aminoacidurias), glucose (renal glycosurias) and bicarbonate (proximal renal tubular acidosis), or for all solutes (Fanconi syndrome) [11].
• Mutations in one of at least eight different genes cause bone marrow failure, chromosome instability, and predisposition to cancer associated with the rare genetic syndrome Fanconi anemia (FA) [12].
• Maleic acid administration produces a defect in tubular reabsorption resembling that seen in the Fanconi syndrome and also causes a decrease in glomerular filtration rate (GFR) [13].
• These data suggest that the generalized membrane transport derangement seen in this experimental Fanconi syndrome could occur via a specific effect on gp330, which seems to block endocytosis and the recycling apparatus at the late endosome level and inhibits the formation of new dense apical tubules [14].

Anatomical context of Fanconi Syndrome

• Proline and glucose transport by renal membranes from dogs with spontaneous idiopathic Fanconi syndrome [7].
• The uptake of proline and glucose by renal brush border membrane vesicles isolated from Basenji dogs exhibiting a spontaneous Fanconi syndrome was examined [7].
• The administration of 1.5 or 9.0 mmoles/kg ip of maleate to rats induced, in addition to renal alterations similar to those occurring in the Fanconi syndrome, a decline in the intestinal mucosa (Na+-K+)-ATPase with a simultaneous decrease in sodium intestinal transport and an increase in potassium absorption [15].
• Dent's disease is an inherited disorder characterized by hypercalciuria, low molecular weight proteinuria, and Fanconi syndrome, which is caused by inactivating mutations in ClC-5, a chloride channel expressed in endosomes of the proximal renal tubule [16].
• Na+,K(+)-ATPase activity and its alpha 1 subunit protein and mRNA in kidney cortex were monitored in rats developing Fanconi syndrome after the administration of maleate [17].

Gene context of Fanconi Syndrome

• CTNS codes for the lysosomal cystine transporter, whose absence leads to intracellular cystine accumulation, widespread cellular destruction, renal Fanconi syndrome in infancy, renal glomerular failure in later childhood, and other systemic complications [18].
• Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome [19].
• Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule [20].
• These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for ClC-5 in the kidney [21].
• One infant, studied prior to the onset of significant renal insufficiency, manifested renal Fanconi syndrome, hyperparathyroidism, and marked hypocalcemia [22].

Analytical, diagnostic and therapeutic context of Fanconi Syndrome

• Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat [23].
• We measured sodium-proton (Na+/H+) exchange in lymphocytes and platelets of a 46-year-old woman with the adult Fanconi syndrome before, during, and after treatment with NaHCO3 [24].
• Occurrence of an acute Fanconi syndrome following cisplatin chemotherapy [25].
• The injection of 200 mg/kg BW maleic acid was found to be a suitable dose for exploring the experimental Fanconi syndrome by micropuncture techniques in rats [26].

References