CYP24A1 Deficiency Presenting With Hypercalcemia and Hypervitaminosis D in Pregnancy: A Case Report

The increasing use of vitamin D supplementation may have unintended consequences for individuals who exhibit heightened sensitivity, leading to supraphysiologic serum vitamin D levels. This is a 32-year-old woman with non-parathyroid hormone-dependent hypercalcemia during pregnancy. Laboratory evaluation showed high 25-dihydroxyvitamin D levels, indicating vitamin D intoxication. Very high calcitriol levels, with a high 25-hydroxyvitamin D:24,25-dihydroxyvitamin D ratio, indicated CYP24A1 deficiency. The patient did not have any history of hypercalcemia, including during prior pregnancies. A homozygous variant of CYP24A1 (c.1490A>C; p.His497Pro) was found. Pregnancy increases the risk of hypercalcemia in individuals with a CYP24A1 mutation by a physiologic increase of 1-α-hydroxylase. Vitamin D and calcium supplementation can be an additional trigger for hypercalcemia in these patients, as seen in our patient. Vitamin D deficiency during prior pregnancies might have been protective from hypercalcemia. This report raises awareness of a subgroup of women at risk for adverse events from vitamin D and calcium supplementation during pregnancy. Checking calcium levels currently is not routine during pregnancy; however, it should be considered more often for symptomatic women.