Endocrine Abstracts

Introduction: Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by increased urinary glucose excretion despite normoglycemia (1). It is most commonly caused by pathogenic variants in the solute carrier family V member 2 (SLC5A2) gene (1-3). This gene encodes the sodium-glucose cotransporter 2 (SGLT2), crucial for glucose reabsorption (1,2).

Case presentation: We report the case of a 44-year-old male who was referred for unexplained glucosuria despite well-controlled diabetes mellitus (HbA1c 6,5%) with metformin and gliclazide therapy. His main complaints were nocturia and unintentional 5-kg weight loss in one year. A 24-hour urinary collection revealed overt glucosuria (23,3 g/1,73 m²/24h), generalized aminoaciduria and increased uric acid excretion (fractional excretion 6,4%). Whole exome sequencing revealed a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene (NM_003041.4). A maturity-onset diabetes of the young type (MODY) gene panel showed no pathogenic variants in the hepatocyte nuclear factor-1A (HNF-1A; MODY3), nor in other MODY-associated genes. We assume that the association of glucosuria, aminoaciduria and hyper-uricosuria can be explained by the combination of diabetes and the likely pathogenic SLC5A2 variant in this patient.

Conclusion: We describe a well-controlled diabetic patient with FRG, associated with a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. Our case highlights the importance of considering renal tubular disorders in patients with unexplained glucosuria and diabetes mellitus, especially if the latter is well-controlled. FRG usually presents with glucosuria but may be associated with generalized aminoaciduria and hyperuricosuria. Genetic analysis should be considered in patients with young-onset diabetes and glucosuria, particularly with a positive familial history.

Referencees: 1. Santer R et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol 14, 2873–82 (2003). 2 Santer R, Calado J. Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin J Am Soc Nephrol 5,133–41 (2010). 3 Wang X et al. Genetic analysis and literature review of Chinese patients with familial renal glucosuria: Identification of a novel SLC5A2 mutation. Clin Chim Acta 469, 105–10 (2017).

Keywords: Glucosuria, SGLT2 mutation, diabetes