Isolated Primary Renal Glucosuria Without SGLT2 Mutation

Introduction: Isolated renal glucosuria is a rare disorder of persistent glucosuria without hyperglycemia, usually caused by SLC5A2 mutations affecting proximal tubule glucose transport. This case is unique because the patient has long-standing isolated glucosuria without hyperglycemia and no detectable mutations in the SLC5A2 gene, suggesting an alternative or unidentified genetic cause. Case Description: A 63-year-old man with stable stage 3 CKD (creatinine 1.52 mg/dL) presented for routine nephrology follow-up. He was asymptomatic but had persistent glucosuria (+50 to +100 mg/dL) on all of his urinalyses dating back many years. He denied diabetes mellitus; HbA1c was normal (mid-5% range). He was not on SGLT2 inhibitors. An oral glucose tolerance test was normal. Family history was unavailable. The patient reported glucosuria at least as far back as age 18, with prior evaluations during military service and commercial truck driving exams confirming glucosuria without diabetes mellitus. Discussion: A 24-hour urine amino acid profile was normal, showing minor reductions in sarcosine and homocysteine, not consistent with aminoacidopathy. Other solutes normally reabsorbed in the proximal tubule were measured in the urine and not excreted in excess. His genetic testing for SLC5A2 (SGLT2) gene mutations was negative. No history of diarrhea or signs of generalized proximal tubule dysfunction were present, making SLC5A1 gene mutation for SGLT1 and Fanconi syndrome unlikely, respectively. GLUT1 Deficiency Syndrome (SLC2A1 mutations) typically presents with neurologic signs in childhood, absent here [1]. Fanconi-Bickel syndrome (SLC2A2 mutations for GLUT2) involves hepatomegaly, fasting hypoglycemia, growth failure, and proximal tubule defects (aminoaciduria, phosphaturia)—none observed in this patient [1]. Given the long-standing isolated glucosuria without systemic or metabolic issues, either familial or spontaneous mutation renal glucosuria is still possible, despite negative SLC5A2 testing. This case is unusual in that the SLC5A2 gene was not altered, and suggests variants in other renal glucose transporters not identified here. Future investigation of other renal glucose transporters might identify the cause. 1. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. (2014). Netherlands: Academic Press.