Fanconi-Bickel Syndrome: Two Pakistani Patients Presenting with Hypophosphatemic Rickets

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Fanconi-Bickel syndrome (FS) is a rare autosomal recessive metabolic disorder.
• It results from defects in the facilitative glucose transporter 2 (GLUT2), encoded by the SLC2A2 gene.
• Clinical manifestations include hepatorenal glycogen accumulation, renal tubular dysfunction, growth failure, and impaired glucose/galactose utilization.

Observation:

• This report details the first two pediatric cases of Fanconi-Bickel syndrome diagnosed in Pakistan.
• Both patients presented with the hallmark clinical features of the syndrome.
• Genetic analysis revealed homozygosity for the c.339delC single nucleotide deletion in the SLC2A2 gene in both individuals.

Findings:

• The identified SLC2A2 mutation, c.339delC, is confirmed as a causative genetic defect in these Pakistani patients.
• This specific mutation was previously documented in an Arab patient with an initial presentation mimicking neonatal diabetes mellitus.
• The findings establish a genetic link for Fanconi-Bickel syndrome in the Pakistani population.

Implications:

• This study expands the geographic and ethnic spectrum of Fanconi-Bickel syndrome.
• It highlights the importance of genetic testing for SLC2A2 mutations in diagnosing FS, especially in cases with atypical initial presentations.
• Early diagnosis and genetic understanding are crucial for managing FS and providing genetic counseling.