Case Report: Two infants with hypercalcemia of rare and distinct etiologies

Objectives Hypercalcemia in infancy is rare and often presents with nonspecific clinical signs, making early recognition challenging. This report describes two infants with severe symptomatic hypercalcemia due to distinct etiologies and highlights the diagnostic value of sterile pyuria as an early clinical clue. Case presentation Both infants presented with nonspecific symptoms, including poor feeding, irritability, constipation, and sterile pyuria. In the first infant the diagnosis of Williams-Beuren syndrome had been established earlier, while the second infant had been previously healthy. Both had demonstrated sonographic evidence of nephrocalcinosis. Laboratory evaluation revealed markedly elevated serum calcium levels (up to 4.73 mmol/L), hypercalciuria, and suppressed PTH concentrations in both cases. Standard treatment of hypercalcemia was ineffective, while a single dose of zoledronic acid led to normalization of calcium levels and complete resolution of symptoms. Subsequent genetic testing in the second infant identified a biallelic pathogenic variant in the CYP24A1 gene, confirming the diagnosis of idiopathic infantile hypercalcemia type 1. During follow-up, neither patient experienced recurrence of hypercalcemia, and renal ultrasound showed improvement or stabilization of nephrocalcinosis. Conclusion Sterile pyuria accompanied by nonspecific symptoms may be an early indicator of hypercalcemia in infants and should prompt calcium evaluation. To our knowledge, this is the first report linking sterile pyuria directly to hypercalcemia in this age group. Zoledronic acid can effectively normalize calcium levels in refractory pediatric hypercalcemia. This report adds to the limited evidence regarding zoledronic acid use in infants with Williams–Beuren syndrome and idiopathic infantile hypercalcemia type 1.