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Abstract: TH-PO384

SGLT2 Inhibitors as a Treatment for Fanconi-Bickel Syndrome: A Case Report

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • D'Ambrosio, Viola, University College London, London, United Kingdom
  • Wan, Elizabeth Rose, University College London, London, United Kingdom
  • Siew, Keith, University College London, London, United Kingdom
  • Walsh, Stephen B., University College London, London, United Kingdom

Group or Team Name

  • London Tubular Centre.
Introduction

Fanconi-Bickel syndrome is an ultra-rare genetic disease characterized by SLC2A2 mutation encoding for the basolateral glucose transporter (GLUT2) in the proximal tubule of the nephron. This defective transport ultimately leads to accumulation of glycogen and dysfunction of proximal tubule cells. This manifests clinically as the renal Fanconi syndrome and eventually kidney failure. Systemic complications of proximal tubule injury include metabolic acidosis, bone demineralization and, for some not completely elucidated reasons, dysglycemia.

Case Description

We present the case of a 43-year-old man who was diagnosed with Fanconi-Bickel syndrome (homozygous splice site mutation in SLC2A2). He had a history of infantile-onset renal Fanconi syndrome, hypercalciuria and bilateral nephrolithiasis, osteoporosis, bilateral sensorineural deafness and non-insulin dependent type 2 diabetes. At referral the patient presented with CKD G2, non-anion gap metabolic acidosis, slightly elevated serum calcium, decreased serum phosphate, supressed PTH and hypercalciuria, despite oral supplementation of phosphate, bicarbonate and vitamin D. We hypothesized that SGLT2i in this patient may halt the progressive proximal tubule injury by preventive glucose uptake and help the management of diabetes. Fractional excretion of phosphate (FEPO4) and urinary retinol-binding protein (RBP)-creatinine ratio, two markers of proximal tubular injury, were stable after 2 months of SGLT2i therapy.

Discussion

To date, Fanconi-Bickel syndrome does not have a specific treatment. Standard of care includes supplements of fluids and electrolytes to counterbalance proximal tubular injury and management of complications such as diabetes. SGLT2i use has been described in a mouse model of another glycogen storage disease (GSD1b), whose underlying defect is different from that of Fanconi-Bickel but presents with a similar phenotype. Data showed that gliflozins prevents glycogen accumulation and restores proximal tubule cells’ function. Using the same rationale, the administration of SGLT2i in adult patients with Fanconi-Bickel syndrome may prevent further proximal damage and slow the progression towards end-stage kidney disease. In conclusion, we hypothesize a potential benefit of SGLT2i in adult patients affected by Fanconi-Bickel syndrome.