ESPE Abstracts

Background: The SGLT2 (Sodium-Glucose Cotransporter 2) protein is responsible for the majority of glucose reabsorption in the proximal tubule. Mutations in SLC5A2, encoding SGLT2, have been first described in 2002, leading to familial renal glucosuria (FRG). Herein we describe the clinical course of an 11-year-old boy in whom a compound heterozygous SLC5A2-mutation was detected, who presented with glucosuria and vomiting with a suspected diagnosis of diabetes.

Case Report: An 11-year-old boy with hitherto unexplained glucosuria (300 - 1.000 mg/dl), known since 5 years, presented with recurrent early morning nausea and vomiting since 3 months. Liquid uptake and urinary output were normal, no weight loss, HbA1c 30 mmol/mol. He was otherwise healthy with normal growth and BMI. Oral glucose tolerance test (oGTT) was pathological (1h blood glucose (BG) 203 mg/dl; 2h BG 160 mg/dl) in the presence of normal fasting BG (89 mg/dl), insulin levels, electrolytes and negative islet cell antibodies (GAD, IAA, IA2). Apart from decreased glucose reabsorption, urine tests were normal. Hyperthyroidism, hypercorticism, growth hormone excess and pheochromocytoma could be ruled out. Brain MRI and abdominal ultrasound were normal. Genetic analysis revealed a compound heterozygous SLC5A2 mutation, inherited from both asymptomatic parents (c.885+5G>A/known; c.1409T>C/novel), the latter leading to a single base pair substitution with very low allele frequency and disrupted SGLT2 function predicted by bioinformatic tools. Oesophagogastroscopy revealed reflux oesophagitis that resolved with PPI treatment. At oGTT reevaluation 6 months later, 2h BG was borderline normal (141 mg/dl) in the presence of normal fasting (89 mg/dl) and 1h BG (135 mg/dl). Renin levels increased significantly after 2h (from 32.5 to 56.1 µU/ml) without change of sodium levels, illustrating activation of the renin-angiotensin-aldosterone system by volume contraction after glucose challenge.

Conclusions: SGLT2-associated FGD represents a perhaps underdiagnosed benign condition. We hypothesize that the unexpected first pathological oGTT result was probably due to significant stress caused by the investigation procedure leading to delayed gastric emptying and/or intestinal absorption, which was further aggravated by reflux oesophagitis.