MON-578 Non-Diabetic Renal Glycosuria: A Rare Case of Heterozygous SLC2A2 c.557 Deletion

Abstract Disclosure: S. Azmat: None. A. Zaidi: None. S. Rabbani: None. D. Kircheva: None. J. Gilden: None. Elevated urine glucose levels are typically due to proximal tubulopathy vs. hyperglycemia with serum glucose levels higher than 200 mg/dl or due to sodium-glucose cotransporter 2 inhibitors use. Familial renal glycosuria is an exceedingly rare disorder characterized by elevated glucose levels in urine with normoglycemia. A rare cause of glycosuria is a genetic mutation in the SLC2A2 gene that disrupts the reabsorption in proximal tubules. We report case of a 36-year-old Jamaican man with non-diabetic renal glycosuria who was found to have a heterozygous SLC2A2 c.557 deletion, a mutation that affects the glucose transporter 2 (GLUT2). Clinical case: A 36-year-old Jamaican male, presented for initial endocrine evaluation for persistent non-diabetic renal glycosuria incidentally found during adolescence. The patient reported polyuria but denied any other associated symptoms of diabetes such as polydipsia or weight loss. There was no known history of urinary tract or other systemic illnesses. There was no reported personal or family history of autoimmune diseases or malignancies. His recent hemoglobin A1c was mildly elevated at 5.9% (4-5.6 %), without prior history of diabetes/prediabetes. Fructosamine, oral glucose tolerance test, and autoimmune workup were ordered to investigate elevated A1c levels and exclude potential DM and autoimmune conditions linked to isolated glycosuria. His serum creatinine was normal 0.98 mg/dL (0.73-1.18), eGFR 103 mL/min/1.73m^2 (>60) with no evidence of proteinuria, urinalysis showed concentrated urine with specific gravity over 1.030 and glucosuria of more than 1000 mg/dl. Serum glucose was 85 mg/dl (70-90), c peptide 0.78 ng/mL( 0.81-3.85); islet cell, GAD 65, zinc transporter & insulin autoantibodies were negative. He was previously seen by nephrology for euglycemic glucosuria and genetic testing confirmed pathogenic heterozygous SLC2A2 c.557 deletion and an uncertain variant in the SLC5A2 gene (c.1433C>T) with 50 % chance of transmission to his offspring. This mutation is believed to result in malfunction of the GLUT2 receptors in the proximal tubules, leading to blockade of glucose reabsorption and glucosuria, a known effect of SGLT2 inhibitor. Due to the lack of evidence that this mutation has any clinical significance, the patient was advised to hydrate well to minimize the risk of dehydration, ketosis, and urinary tract infections. Conclusion: This is a rare case of euglycemic renal glycosuria in the absence of SGLT2 inhibitor use or other evidence of proximal tubulopathy. Genetic testing confirmed a heterozygous SLC2A2 c.557 deletion. This report contributes to the rare incidence of genetic renal glycosuria that prompted further investigation for other autoimmune conditions, which may be associated with this mutation. In addition, it is important to recognize that not all cases of glycosuria are due to diabetes mellitus. Presentation: Monday, July 14, 2025