CYP24A1 mutation as a rare cause of hypercalcemia during pregnancy

Liisa Kullamaa; Sanni SOderlund; Marianna Viukari; Niina Matikainen; Camilla Schalin-Jantti

doi:10.1530/endoabs.90.RC8.3

Clinical case: A 27-year-old pregnant woman (24 weeks of gestation) was investigated as her Hb level (87 g/l) was low. Laboratory work-up revealed severe, non-PTH dependent hypercalcemia (see Table). This was her first pregnancy, and serum calcium measured once previously 12 years earlier had been normal. The patient had symptoms of increased thirst, constipation and hyperemesis.

Diagnostic work up and Treatment: Rehydration and close monitoring of calcium concentration was initiated. Hematological investigations, including bone marrow biopsy, were normal. Whole body MRI did not reveal any malignancy. In addition to PTH, PTHrp concentration was also suppressed. The patient was put on oral prednisolone, but the effect was not sustained. Next, genetic causes of hypercalcemia during pregnancy were considered. Both FHH and MEN-1 syndrome are characterized by PTH-dependent hypercalcemia. A CYP24A1 mutation was suspected, and low-calcium diet was initiated on the 30^th gestational week, before the results of genetic analysis were obtained. Mutation screening of the CYP24A1 gene revealed a homozygous inactivating mutation c.1186C>T; p.(Arg396Trp). The patient was started on a diet strictly avoiding both calcium and vitamin D, which lowered her serum calcium to a nadir of 1.28 mmol/l/pH7.4. The fetus was regularly monitored during pregnancy and no signs of growth retardation were noted. The patient delivered a healthy child at 38 weeks of gestation. After delivery, the patient’s calcium levels remained normal on a regular diet. The patient’s sister was found to be heterozygous for the same gene mutation. Her calcium levels remained normal during pregnancy.


Lab	Result	Reference range
S-Ca-ion	1.76 mmol/l/pH7.4	1.16-1.3
eGFR	66 ml/min/1.73 m²	>89
24-h U-Ca	11.72 mmol	1.3-6.5
fP-PTH	<4.6 ng/l	18-80
P-PTHrP	<0.50 pmol/l	<1.3
S-D-25	84 nmol/l	>50
S-D-1,25	238 pmol/l	48 – 190
S-LZM	15 mg/l	<12

Discussion: During pregnancy, intestinal calcium absorption in the mother almost doubles to ensure the requirements of the fetus, which is mediated by increased S-D-1,25 and estrogen concentrations. Inactivating mutation in CYP24A1, encoding vitamin D-24-hydroxylase, can further accumulate active vitamin-D metabolites and present as hypercalcemia during pregnancy. In addition, the amount of vitamin D and calcium supplements used may influence calcium concentrations during pregnancy.

Endocrine Abstracts

RC8.3