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Kidney Week

Abstract: FR-PO600

Heterozygous Pathogenic Variants in SLC34A3 in Patients with Recurrent Calcium Phosphate Kidney Stones

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Sohail, Mohammad Ahsan, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States
  • Wang, Xiangling, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States
  • Calle, Juan C., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States
  • Ferreira Provenzano, Laura, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio, United States
Introduction

The solute carrier family 34-member 3 (SLC34A3) gene encodes the renal type 2c sodium-phosphate cotransporter and mutations in SLC34A3 cause an autosomal recessive disorder known as hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Disease onset is typically observed in infancy/childhood and is associated with hypophosphatemia, growth retardation, rickets and/or osteomalacia. There is also an adult-onset form recognized in heterozygous carriers of SLC34A3 variants with manifestations of reduced bone density and multiple fractures. Here we describe two adult patients with heterozygous pathogenic variants in SLC34A3, who presented with recurrent calcium phosphate nephrolithiasis without hypophosphatemia or bone disease.

Case Description

Case 1: A 47-year-old female with type 2 diabetes mellitus, migraine headaches on topiramate and a paternal history of nephrolithiasis was evaluated by renal genetics for recurrent kidney stones. As shown in Table 1, she had hypercalciuria, hypocitraturia and urine pH of 6-7. Calculus analysis revealed 90% calcium phosphate composition. Genetic testing showed a heterozygous pathogenic variant in SLC34A3 (c.1304del).
Case 2: A 46-year-old female with morbid obesity S/P sleeve gastrectomy 4 years ago presented for renal genetics evaluation for recurrent kidney stones since age 18. As shown in Table 1, she had hypercalciuria, hypocitraturia despite potassium citrate, hyperoxaluria and urine pH of ≥7. Multiple calculi analyses revealed 78-90% calcium phosphate composition. Genetic testing showed a heterozygous pathogenic variant in SLC34A3 (c.1046_1047del).

Discussion

Our patients seemed to have a predilection for developing calcium phosphate stones, and to our knowledge, this has not been previously recognized in the literature in patients with heterozygous pathogenic variants in SLC34A3. Both cases presented with hypercalciuria, hypocitraturia and alkaline urine pH. The association of SLC34A3 gene variants with calcium phosphate stone formation deserves further investigation.

Table 1
Laboratory DataCase 1Case 2
Urine Calcium / 24 hours (mg) (range)390 - 450232 - 315
Urine Citrate / 24 hours (mg) (range)207 - 454< 40
Urine Oxalate / 24 hours (mg) (range)22 - 3052 - 60
Urine pH (range)6 - 7≥ 7
Serum Phosphorus (mg/dL) (range)3.0 - 3.53.2 - 3.4