FAMILIAL GATM-ASSOCIATED FANCONI SYNDROME WITH PROGRESSIVE CKD

Abstract

Fanconi syndrome is a generalized proximal tubular disorder characterized by urinary wasting of bicarbonate, phosphate, glucose, amino acids, and other solutes. Hereditary forms are uncommon and are increasingly recognized with advances in molecular diagnostics. We report familial Fanconi syndrome associated with a heterozygous glycine amidinotransferase (GATM) variant, demonstrating a phenotypic spectrum from infancy to adulthood. A female infant presented with failure to thrive, hypophosphataemic rickets, glycosuria without hyperglycaemia, and normal anion gap metabolic acidosis consistent with proximal tubular dysfunction. Her father had childhood-onset renal rickets with progressive skeletal deformities requiring multiple orthopaedic procedures and subsequently developed chronic kidney disease (CKD). Whole-exome sequencing in the child identified a heterozygous GATM variant, c.1084G>C (p.Val362Leu), which was confirmed in the father by Sanger sequencing. Co-segregation of the variant with the phenotype across two generations supports possible pathogenic relevance. This report highlights the importance of considering hereditary proximal tubulopathies in children with rickets and normal vitamin D levels and illustrates the possible progression from isolated tubular dysfunction to chronic structural kidney disease in GATM-associated disease.