Fanconi-Bickel syndrome as an example of marked allelic heterogeneity.

ABSTRACT: Renal tubular acidosis (RTA) encompasses many renal tubular disorders characterized by hyperchloremic metabolic acidosis with a normal anion gap. Untreated patients usually complain of growth failure, osteoporosis, rickets, nephrolithiasis and eventually renal insufficiency. Fanconi-Bickel syndrome (FBS) is an example of proximal RTA due to a single gene disorder; it is caused by defects in the facilitative glucose transporter 2 gene that codes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic ?-cells, enterocytes and renal tubular cells. It is a rare inherited disorder of carbohydrate metabolism manifested by huge hepatomegaly [hence it is classified as glycogen storage disease (GSD) type XI; GSD XI], severe hypophosphatemic rickets and failure to thrive due to proximal renal tubular dysfunction leading to glucosuria, phosphaturia, generalized aminoaciduria, bicarbonate wasting and hypophosphatemia. The disorder has been reported from all parts of Europe, Turkey, Israel, Arabian countries, Japan and North America. Many mutant alleles have been described, its exact frequency is unknown and there is no single mutation found more frequently than the others. The presence of consanguinity in affected families suggests an autosomal recessive pattern of inheritance. New cases of FBS have been recently reported in the Middle and Far East in collaboration with specialized centers. Two novel mutations have been discovered in two unrelated Egyptian families. The first was two bases deletion, guanine and adenine, (c.253_254delGA) causing a frameshift mutation (p. Glu85fs) and the second is mutation in exon6 in splicing acceptor site with intron5 (c.776-1G>C or IVS5-1G>A). Moreover, a new different mutation was described in a 3 year old Indian boy.

SUBMITTER: Al-Haggar M 

PROVIDER: S-EPMC3782201 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature