Hepatomegaly, Rickets, and Proximal Tubulopathy in a Child with a Homozygous SLC2A2 Missense Variant of Uncertain Significance -A Paediatric Case Report

Background: Fanconi–Bickel syndrome (FBS, OMIM #227810) is a rare autosomal recessive disorder of carbohydrate metabolism caused by biallelic pathogenic variants in SLC2A2, the gene encoding the facilitative glucose transporter GLUT2. It is characterised by hepatorenal glycogen accumulation, generalised proximal renal tubular dysfunction (renal Fanconi syndrome), and impaired utilisation of glucose and galactose. Case Presentation: We describe a male child, born of a non-consanguineous marriage, who presented in later childhood with short stature, chronic malnutrition, genu valgum, widened wrists, poor growth, polyuria and difficulty in walking. Biochemical evaluation showed hypophosphatemia, decreased tubular phosphate reabsorption, glucosuria, generalised aminoaciduria, elevated serum alkaline phosphatase and radiological/biochemical features of rickets, findings consistent with proximal renal tubular (Fanconi) syndrome. Serum ceruloplasmin was normal, making Wilson disease unlikely, and renal ultrasonography was unremarkable. Genetic Findings: Clinical exome/targeted next-generation sequencing identified a homozygous missense variant in SLC2A2, NM_000340.2:c.353T>C (p.Leu118Pro), currently classified as a variant of uncertain significance (VUS) but phenotypically consistent with Fanconi–Bickel syndrome. In-silico predictors supported a deleterious effect (REVEL 0.826; CADD 29.2), the variant was absent from population databases, and both unaffected parents were presumed obligate heterozygous carriers, consistent with autosomal recessive inheritance. Conclusion: This case illustrates the diagnostic value, and the interpretive challenges, of next-generation sequencing in rare metabolic-renal disorders of childhood. Robust clinical–biochemical correlation remains essential when a candidate variant is reported as a VUS, and periodic reclassification and multidisciplinary (nephrology, genetics, endocrinology) follow-up is recommended.