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Abstract: PO2310

Variants of SLC34A1, SLC34A3, and AGXT in an Infant with Nephrocalcinosis and Hypercalcemia

Session Information

Category: Trainee Case Report

  • 1700 Pediatric Nephrology

Authors

  • Wright, Mariah L., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Mahan, John D., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Mohamed, Tahagod, Nationwide Children's Hospital, Columbus, Ohio, United States
Introduction

Idiopathic infantile hypercalcemia (IIH) is a rare genetic disorder that can lead to neonatal nephrocalcinosis. It is typically caused by loss of function mutations in CYP24A1 or less commonly in SLC34A1. SLC34A1 encodes the NaPi-IIa transporter which aids in phosphate reabsorption in the renal proximal tubules. Defects in AGXT are responsible for primary hyperoxaluria type 1 (PH1). Defects in either AGXT or SLC34A1 can lead to infantile nephrocalcinosis and subsequent renal damage.

Case Description

A term male infant had bilateral hyperechoic kidneys on prenatal ultrasound. Postnatal labs showed hypercalcemia, hypophosphatemia, high 1,25 dihydroxyvitamin D3 and acute kidney injury. The patient was treated with fluids, furosemide, and calcitonin without significant change in serum calcium. Pamidronate was given which decreased serum calcium and worsened hypophosphatemia. Phosphate supplementation was initiated. Whole exome sequencing revealed two variants in SLC34A1, one of which was pathogenic, and a variant in SLC34A3 of unknown significance. Incidentally, this patient was compound heterozygous for three variants in AGXT: one pathogenic and two benign. After these results, patient was found to have generalized aminoaciduria and mild hyperoxaluria for age. Serum calcium decreased with maintenance of adequate plasma phosphate levels.

Discussion

Compound heterozygous mutations of SLC34A1 can cause IIH type II, and the variant in SLC34A3 could be contributing to this patient’s clinical phenotype in a unique trialleic pattern. The pathologic AGXT gene variants could cause this patient to develop PH1. The combined effects of IIH and PH1 could significantly impact the clinical course of this patient. Mutations in both AGXT and SLC34A1 have not been previously described in the literature. During acute severe hypercalcemia, it might be necessary to use pamidronate to lower serum calcium to levels that are safe for the administration of phosphate supplements.

EventsDays after initial presentationCalcium (8.0-10.5 mg/dL)Phosphorus (4.2-6.5 mg/dL)1,25 Dihydroxyvitamin D3 (15-90 pg/nL)25-Hydroxyvitamin D (30-120 ng/mL)
Initial Presentation1153.33218
After 1st Pamidronate infusion1011.22.3  
 2311.24  
After 2nd Pamidronate infusion2410.53.6  
After Phosphate Supplementation479.65.221224
 7510.54.4  
 13810.4512234