Describe management of hypercalcaemia due to CYP24A1 mutation throughout pregnancy and the puerperium.
The CYP24A1 gene encodes 24-hydroxylase which metabolises 1,25OH vitamin D. Inactivating CYP24A1 mutations were first identified as causing idiopathic infantile hypercalcaemia in 2011. More recently this mutation has been described in adults with hypercalcaemia. Pregnancy appears to exacerbate hypercalcaemia due to increased synthesis of 1,25OH Vitamin D. Case reports describe 9 pregnancies in 3 women with CYP24A1 mutations, demonstrating worsening hypercalcaemia and significant complications such as FDIU, pre-term delivery, IUGR and pre-eclampsia.[2-4] Management strategies for this condition in pregnancy, including the use of calcitonin, have not been described.
A 32-year-old female (G2P1) with known CYP24A1 mutation and stage 1 chronic kidney disease (nephrocalcinosis) presented at 14/40 with recurrent hypercalcaemia (iCa 1.44mmol/L 1.13-1.32mmol/L) and mild acute on chronic kidney injury (AKI).
Her first pregnancy was complicated by term pre-eclampsia, post-partum AKI and severe hypercalcaemia. Neonatal hypercalcaemia prompted genetic diagnosis in the patient and her son. The genetic status of the second foetus was unknown.
Parathyroid hormone suppression and elevated serum 1,25-OH Vitamin D were confirmed.
Hypercalcaemia was initially managed with high oral fluid intake, oral corticosteroids and potassium citrate. Cyclical Calcitonin (100iU bd) was introduced to target serum ionised calcium of 1.3-1.35mmol/L from 22 weeks to maintain a physiologic intrauterine environment and prevent maternal/neonatal complications.
Figure 1 and 2 show relevant biochemical parameters during pregnancy.
A healthy male neonate was delivered at 38+5/40 by elective repeat LUSCS without need for treatment of electrolyte abnormalities at one week of age (follow-up ongoing). The patient elected not to breastfeed.
Persistent vitamin D-mediated maternal hypercalcaemia was effectively managed with calcitonin avoiding maternal and fetal complications.
1. Schlingmann, NEJM, 2011.
2. Dinour, Pediatr Nephrol, 2015.
3. Shah, J Clin Endocrinol Metab, 2015.
4. Woods, J Bone Miner Res, 2016.