A Rare Genetic Variant in SLC2A2 c.682 C > T (p.Arg228Ter) Underlying Complex Tubular Dysfunction and Progressive Bone Disease in Fanconi–Bickel Syndrome: A Novel Mutation with Systemic Implications

Abstract

Background: Fanconi–Bickel Syndrome (FBS) is a rare metabolic disorder caused by pathogenic variants in the SLC2A2 gene, leading to defective glucose transport and characteristic hepatorenal glycogen storage. We report a 3‑year‑old male presenting with failure to thrive, progressive abdominal distension, rickets, and biochemical evidence of proximal renal tubular dysfunction, including hypophosphatemia, metabolic acidosis, glucosuria, and hypouricemia.

Results: Exome sequencing revealed a homozygous nonsense variant, NM_000340.2 (SLC2A2):c.682C>T (p.Arg228Ter), classified as pathogenic and consistent with Fanconi–Bickel Syndrome. The patient was managed with oral phosphate and bicarbonate supplementation, along with nutritional rehabilitation. Despite good adherence, serum phosphate levels remained low, and there was limited improvement in growth velocity and skeletal deformities, highlighting the chronic and refractory nature of the disease.

Conclusions: Early genetic diagnosis is essential in children presenting with refractory rickets and renal tubular dysfunction. Identification of the novel p.Arg228Ter variant expands the known mutation spectrum of SLC2A2 and supports genotype–phenotype correlations. Timely molecular confirmation facilitates prognosis assessment, genetic counseling, and multidisciplinary care planning in affected families..