A Novel SLC9A3R1 Mutation as a Rare Cause of Infantile Hypercalcemia

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 <i>(</i>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.