Fluconazole as a New Therapeutic Tool to Manage Patients With NPTIIc (SLC34A3) Mutation: A Case Report.

Mutations in the SLC34A3 gene, encoding the sodium/phosphate cotransporter 2C (NPTIIc), induce decreased renal phosphate reabsorption, hypophosphatemia, decreased fibroblast growth factor 23 and parathyroid hormone, and increased 1,25-dihydroxyvitamin D (1,25[OH]D) levels. The complete phenotype is characterized by hypophosphatemia, hypercalciuria, and nephrolithiasis/nephrocalcinosis, leading to chronic kidney disease and osteoporosis in adults. We report a 15-year-old boy referred for nephrocalcinosis. The patient demonstrated hypercalcemia, hypercalciuria, normal serum phosphate level, normal tubular phosphate reabsorption, and increased serum 1,25(OH)D level with suppressed serum parathyroid hormone. Compound heterozygous mutations in SLC34A3 were found. Hydrochlorothiazide failed to decrease calciuria. Fluconazole, an inhibitor of 1α-hydroxylase, was effective in normalizing calciuria without decreasing glomerular filtration rate. We conclude that children with SLC334A3 mutations can present with a less-typical phenotype, having normal serum phosphate levels and normal renal phosphate reabsorption. Genetic abnormalities of NPTIIc should be considered in cases of increased 1,25(OH)D levels without mutations in CYP24A1. The utility of fluconazole to decrease 1,25(OH)D levels requires confirmation in larger studies.