# A Novel SLC9A3R1 Mutation as a Rare Cause of Infantile Hypercalcemia

## TL;DR

A rare infant case of hypercalcemia was caused by a new mutation in the SLC9A3R1 gene, showing how genetic testing can help diagnose and treat rare conditions early.

## Contribution

A novel SLC9A3R1 mutation is identified as a rare cause of infantile hypercalcemia and NPHLOP2.

## Key findings

- A two-month-old infant with hypercalcemia was found to have a heterozygous SLC9A3R1 missense variant.
- The patient showed clinical improvement after treatment with zoledronic acid and dietary adjustments.
- Genetic testing confirmed a diagnosis of hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2).

## Abstract

Hypercalcemia in infants is a rare but potentially serious condition characterized by elevated serum calcium levels. We report a case of a two-month-old female presenting with poor feeding, lethargy, irritability, and failure to thrive, and she was found to have hypercalcemia. On examination, she had a weight of 3.1 kg (-3.94 SDS) with normal facial features. Laboratory investigations revealed elevated serum calcium, low phosphate, suppressed parathyroid hormone (PTH), and high 1, 25-dihydroxyvitamin D levels. Renal ultrasonography revealed bilateral medullary nephrocalcinosis. Clinical exome sequencing identified a heterozygous missense variant in the SLC9A3R1 gene, leading to a diagnosis of hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2). She was initially managed with calcium restricted diet, intravenous fluid rehydration, and administration of zoledronic acid. On follow-up at one month, the patient showed significant symptomatic improvement with normalization of serum calcium levels along with weight gain. This case highlights the role of genetic testing to identify rare genetic causes of hypercalcemia during infancy. Early diagnosis and appropriate management of NPHLOP2 can significantly improve an individual's outcomes and quality of life.