Hypercalcemia in pregnancy secondary to pathogenic variants in CYP24A1

Hypercalcemia is rare in pregnancy and carries a significant risk for both mother and fetus. A rare cause of hypercalcemia is loss-of-function mutations in CYP24A1, which encodes 24-hydroxylase, responsible for the inactivation of active vitamin D metabolites. Pregnancy-associated upregulation of 1α-hydroxylase, increased parathyroid hormone (PTH)-related peptide, and supplementation with vitamin D can unmask CYP24A1 deficiency. This condition should be suspected in women presenting with unexplained hypercalcemia, suppressed PTH, and a negative secondary workup for malignancy, granulomatous disease, and contributory medications. Management includes intravenous fluids, calcitonin, and avoidance of vitamin D and calcium supplements. Here, we report a case of persistent hypercalcemia despite aggressive hydration and calcitonin therapy. Postpartum genetic testing confirmed a homozygous CYP24A1 mutation, with markedly elevated 1,25(OH)₂D levels. CYP24A1 mutations are a rare but important cause of gestational hypercalcemia. Early recognition and multidisciplinary management can improve maternal and neonatal outcomes.