CYP24A1 gene defect manifesting with gestational hypercalcemia

Hypercalcemia is a rare condition in pregnancy. It is most commonly caused by primary hyperparathyroidism and parathyroid hormone-related peptid (PTHrP)-producing malignant tumours, less frequently by increased intestinal calcium absorption, vitamin D intoxication, milk-alkali syndrome, and granulomatous diseases or lymphomas, in which vitamin D 1 alpha-hydroxylase expression is increased. Rarely, gestational hypercalcaemia may be caused by a disorder of vitamin D catabolism caused by loss-of-function mutations in the CYP24A1 gene. We report the case of a 34-year-old Caucasian female patient. She was diagnosed with hypercalcaemia, normal intact parathyroid hormone (PTH) level and lower left parathyroid adenoma. Investigations for malignancy showed no evidence of abnormality. The lower-left parathyroid adenoma was removed followed by cessation of hypercalcaemia. Fifteen months later, she had a spontaneous miscarriage at a gestational age of 8 weeks, when serum calcium was at the upper limit of normal. 25 months following parathyroid surgery, as a 12-week pregnant, our patient manifested with symptomatic, PTH-independent hypercalcaemia. 25-hydroxy-vitamin-D and PTHrP were within reference ranges while 1,25(OH)2D level was clearly elevated. Compound heterozygosity within the CYP24A1 gene was confirmed. By conservative treatment, no other complications were observed during pregnancy, and she finally gave birth to a healthy girl with a term. We present the difficulties of diagnosing and treating hypercalcaemia observed during pregnancy. According to our knowledge, our patient represents the first case of CYP24A1 gene defect diagnosed in Hungary.