Valproic Acid-Induced Fanconi Syndrome: A Diagnostic Challenge

Introduction: Fanconi syndrome (FS) is a rarely reported adverse effect of valproic acid (VPA) use. Prompt diagnosis can prove challenging in medically complex patients. Case Description: A seven-year-old male with a history of cystic fibrosis (CF), neonatal hypoxic-ischemic encephalopathy, epilepsy, developmental delay, spastic quadriplegic cerebral palsy, and gastrojejunostomy tube dependence presented to the emergency department with diarrhea, bruising, and fatigue. Initial workup revealed hypokalemia (2.0 mmol/L), hypophosphatemia (0.5 mg/dL), thrombocytopenia (57 K/uL), proteinuria (300 mg/dL), and glycosuria (250 mg/dL). He was admitted to the hospital for laboratory monitoring and electrolyte repletion. Electrolyte derangements were initially attributed to diarrhea and CF-related chronic malabsorption. His case was also complicated by an open Child Protective Services investigation filed by his outpatient CF team for suspected medical neglect due to persistent vitamin deficiencies, prompting concern for refeeding syndrome from suspected chronic malnutrition. He was evaluated by endocrinology for CF-related diabetes due to glycosuria, but had normal hemoglobin A1c and negative urine ketones. The nephrology team was consulted on day four of admission and urine studies revealed an inappropriately elevated fractional excretion of phosphorus (136%) and elevated urine microalbumin to creatinine ratio (307 mg/g). His hypophosphatemia with concurrent phosphaturia, glycosuria, and tubular proteinuria was diagnostic of Fanconi syndrome. Review of his medications identified VPA as the likely causative agent with a recent history of increased VPA dosing for breakthrough seizures. VPA was tapered off and he started phenobarbital for seizure control. He started daily PHOS-Na-K, potassium chloride, and cholecalciferol supplementation and has had normal electrolytes at outpatient nephrology follow-up appointments. Discussion: This case illustrates the challenge of identifying VPA-induced FS in a medically complex patient with multiple potential causes of electrolyte derangements. As VPA-induced FS has been reported almost exclusively in patients with significant medical comorbidities, it is important to maintain a high index of suspicion for FS and perform a thorough diagnostic workup when these patients present with persistent electrolyte abnormalities.