SAT145 Familial Renal Glycosuria - A Differential Diagnosis For Hypoglycemia

Abstract

Abstract Disclosure: S. Syed: None. S. Naqvi: None. L. Menon: None. J. Holthoff: None. A.R. Kasireddy: None. S. Alshami: None. Background: Familial renal glycosuria can be an uncommon cause of hypoglycemia. We present the case of a woman who was referred to the endocrinology clinic for further evaluation of hypoglycemia and was found to have familial renal glycosuria due to a novel mutation in the solute carrier family 5 member 2 (SCL5A2) gene. Case presentation: A 24 year-old woman with past medical history of rheumatoid arthritis, hyperlipidemia and renal glycosuria presented for persistent hypoglycemia. She first started noticing these episodes four years ago and they have increased over the last year. These events occur in the early hours of the morning or overnight despite a high carbohydrate meal at bedtime. She had the following labs: fasting C-peptide 1.04 (0.9-4.3 ng/ml), insulin 4.1 (2.4-21.8 microU/ml), fasting glucose 84 (70-110 mg/dl) and HbA1c 4.8%. DEXCOM download showed hypoglycemic episodes 2-3 hours after meals. On urinalysis, glucose was >1000 mg/dl and a 24 hour urine collection for glucose was 16.8 g/24 hours. She was first diagnosed with asymptomatic glycosuria during her first pregnancy 7 years ago but the cause was never investigated. After seeing endocrinology, she was referred to nephrology who ordered further workup. Initial markers of a complete Fanconi syndrome were normal: urine pH 5.5, magnesium and phosphorus were normal. Genetic testing was done and the patient was found to have a missense mutation in the SCL5A2 gene which results in a single amino acid substitution of Arg to Cys at codon 60 in exon 2 and encodes the SGLT2 protein. On review of literature, this particular mutation has never been reported and the inheritance pattern is likely to be autosomal dominant since she had a heterozygous mutation. The hypoglycemia was noted to be reactive and occurred after meals. She was advised to avoid simple sugars which can precipitate reactive hypoglycemia within a couple of hours of eating foods with a high glycemic index. She also has a bicornuate uterus and history of recurrent urinary tract infections. Out of her 4 children, two have omphalocele and genetic analysis showed that they are recessive carriers for Smith-Lemi-Optiz syndrome. One of those children suffered from hypoglycemia following birth with prolonged NICU stay. No urinalysis or genetic analysis is available for that child. Her third child was born premature and had hydronephrosis. Conclusion: In literature, a total of 86 mutations of the SLC5A2 gene have been reported to be associated with familial renal glycosuria. There are case reports on some of these mutations also causing hypoglycemia. Our case highlights that renal glycosuria should be considered as a differential when evaluating patients with hypoglycemia since these may be correlated. The patient had a novel mutation causing glycosuria, hypoglycemia and could be associated with congenital malformations. More studies on this association are needed. Presentation: Saturday, June 17, 2023