Isolated Glucosuria in a Patient with SLC5A2 Mutation

Introduction: Isolated glucosuria occurs in the absence of elevated glucose levels. It can be caused by inherited defects in addition to acquired conditions. Case Description: A 60-year-old female presented with urine glucose 1000mg/dL since high school despite normoglycemia. She had a history of recurrent genital yeast infections and polyurea. She denied prior chemotherapy, heavy metals, Cisplatin, ifosfamide, tenofovir, or intake of vitamin C. Family history included diabetes mellitus but no familial glucosuria. The patient was normotensive, with a high BMI. Evaluation excluded diabetes mellitus, renal dysfunction, proximal tubulopathies. SPEP, ANA/Anti DNA, copper/ceruloplasmin were negative. Urine sodium was 68mmol/L, Urine osmolality was 656 mOsm/kg, 24 hour urine for glucose was 61, 336mg. Genetic testing revealed an autosomal recessive, homozygous SLC5A2 (Solute Carrier Family 5 Member 2) mutation encoding the sodium-glucose cotransporter SGLT2, the variant was identified as c.1152_1163del (p. Val385_Ala388del). Discussion: SLC5A2 mutations disrupt the sodium-glucose cotransporter SGLT2 and cause familial renal glucosuria (FRG), a rare autosomal recessive/dominant condition impairing renal glucose reabsorption despite normal glucose levels. The estimated prevalence of Familial Renal Glucosuria (FRG), which is primarily caused by SLC5A2 mutations, is around 1 in 33,000. There are 111 different SLC5A2 variants associated with FRG.SGLT2 is responsible for reabsorbing up to 90% of filtered glucose in the proximal convoluted tubule. Heterozygous individuals typically exhibit mild glucosuria (<10 g/day), while homozygous cases show severe excretion (>60 g/day). Complications (e.g., UTIs, hypotension) are rare. FRG may confer partial diabetes protection due to reduced renal glucose reabsorption, though cases with concurrent diabetes exist. The clinical spectrum can range from asymptomatic glucosuria to mild volume depletion and salt wasting. Growth and renal function remain normal. SGLT2 inhibitors remain effective in coexistent diabetes. SGLT2 inhibitors have shown benefits in reducing cardiovascular events and slowing the progression of kidney diseases in patients with type two diabetes mellitus. Although recently a variant of SCL5A2 has been described with a reduced risk of cardiovascular outcomes, it is unclear whether the presence of this genetic mutation has a meaningful cardio-renal protective effects.