ESPE Abstracts

Background: Mutations in the SLC2A2 gene are implicated in Fanconi-Bickel syndrome (FBS). This is a rare form of glycogen storage disease (GSD) inherited in an autosomal recessive manner characterized by hepato-renal glycogen accumulation, impaired glucose and galactose utilization, and proximal renal tubular dysfunction. The world-wide frequency of Fanconi-Bickel syndrome is not known, though the disease is considered to be rare in which a little more that 100 cases have been reported in the literature. Interestingly, there is no FBS cases described from Qatar.

Objective(s): To describe the clinical and genetic characteristics of a FBS patient with a novel mutation encoding the SLC2A2 gene.

Case report: The patient presented with renal tubular acidosis, recurrent spontaneous pathological fractures and short stature. On examination, her weight was 23 kg (<5th percentile) and height of 100 cm (<5th percentile). She had thoracolumbar scoliosis and multiple deformities in the upper and lower limbs, leading to limited ambulation. Biochemically there was hypophosphatemia, hypocalcemia, elevated alkaline phosphatase and liver enzymes (ALT and AST). Fasting hypoglycemia and postprandial hyperglycemia were identified. Urine analysis was significant for phosphaturia, and evidence of proximal renal tubular acidosis (RTA) indicated by generalized aminoaciduria. The patient was diagnosed with diabetes mellitus at the age of 17 years and is currently on insulin.

Methods/results: Using genomic DNA Whole Exome Sequencing (WES) analysis was performed. The exonic region and flanking splice junctions of the genome were captured and sequenced by NetGen sequencing on an Illumina system. Sequence and copy number variations were described according to the Human Genome Variation Society (HGVS) and International System for human Cytogenetic Nomenclature (ISCN) parameters, respectively. Whole Exome Sequencing showed c.613-7T>G: IVS5-7T>G in intron 5 in the SLC2A2 gene. This variant reduces the quality of the splice acceptor site in intron 5 and creates a new cryptic splice acceptor site upstream of the natural splice site.

Conclusions: We report a novel mutation in the SLC2A2 gene in a FBS patient. The molecular mechanism/s underlying some of the biochemical and clinical features of FBS are not well understood and currently there is no effective treatment for the underlying genetic defect. Further research is focusing on developing novel therapies for these patients with FBS.