Infantile Nephrocalcinosis Resulting From a Pathogenic CYP24A1 Mutation

Hypercalcemia is a rare finding in children but is most common in neonates.1 Unlike adults, in whom the vast majority of cases are due to hyperparathyroidism and malignancy, the etiology of childhood hypercalcemia is diverse and commonly presents with nonspecific signs and symptoms.1, 2 Despite the often subtle and nonspecific presentation, left untreated it can lead to serious end-organ injury. As a result, prompt and thorough workup of children with hypercalcemia is extremely important. Calcium homeostasis is maintained through the interaction of parathyroid hormone and vitamin D. Vitamin D accomplishes its primary function by maintaining normal calcium and phosphorus balance through careful regulation of active metabolites. Vitamin D is supplied to the body either as a supplement or through endogenous photolysis of precursors in the skin to the 2 primary forms of inactive vitamin D: vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). These inactive forms are first metabolized in the liver by 25-hydroxylase (CYP2R1) to 25-hydroxy-vitamin D3. This enables the critical second hydroxylation by 1α-hydroxylase (CYP27B1) in the kidney to generate the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3. When calcium is sufficient, 24-hydroxylase (CYP24A1) leads to reduced 1,25-dihydroxyvitamin D3 levels by converting it to 1,24,25(OH)3D3, which is eventually excreted as calcitroic acid.3, 4, 5 Nephrocalcinosis is a rare etiology of kidney disease in infants but, when present, raises an important differential diagnosis. We present a case of infantile nephrocalcinosis due to a novel pathogenic mutation in CYP24A1.