SAT252 Homozygous CYP24A1 Gene Mutation Induced Hypercalcemia During Pregnancy

Abstract

Abstract Disclosure: A.R. Ankireddypalli: None. H. Alameddine: None. Introduction: The approach and management of hypercalcemia in pregnancy can be challenging. Pregnancy challenges the calcium homeostasis with physiological increase in 1,25 dihydroxy Vitamin D levels by kidneys and placental 1-alpha hydroxylase, however it rarely causes hypercalcemia. In PTH independent hypercalcemia, disorders in vitamin D metabolism should be considered. Here we report a case of PTH independent hypercalcemia due to autosomal recessive homozygous CYP24A1 gene mutation. Case: A 25-year-old primigravid female presented to the clinic at 26 weeks of gestation for management of hypercalcemia. At 25 weeks gestation, laboratory workup revealed calcium: 13.9 mg/dL, albumin: 2.9 g/dL, PTH: < 6 pg/mL, vitamin D: 45.17ng/mL, creatinine: 1.02 mg/dL, alkaline phosphatase (ALP): 117mcg/L. Since getting pregnant she reported nausea and vomiting. She reported excessive thirst, memory loss, fatigue, exertional dyspnea and 10 lbs weight loss. She denied any personal history of kidney stones or family history of calcium or bone disorders. She stopped her prenatal vitamins at the time of hypercalcemia diagnosis. Her work-up was suggestive of PTH independent hypercalcemia. Differential diagnosis included granulomatous disease, malignancy, benign PTHrP secreting tumors, vitamin D metabolism dysfunction and milk-alkali syndrome. Further work-up revealed ionized calcium: 6.2 mg/dL, PTHrP: 5.3 pmol/L, bone specific ALP: 11.8 mcg/L, 25 hydroxy vitamin D: 132 mcg/L, 1, 25 dihydroxy vitamin D: > 200 pg/mL, 24,25 dihydroxy vitamin D: 1.16 ng/mL, 25-hydroxy vitamin D to 24,25 dihydroxy vitamin D ratio: 75.0, which was indicative of CYP24A1 mutation, an enzymatic defect in vitamin D metabolism. Molecular testing confirmed autosomal recessive homozygous CYP24A1 gene mutation. With elevated 24,25 dihydroxy vitamin D levels, it was unlikely that her 1,25 dihydroxy vitamin D was elevated due to malignancy or granulomatous disease. Treatment with prednisone 60 mg daily for 1 month did not improve her calcium levels. She was recommended to limit her calcium intake, avoid vitamin D supplements or sun exposure. At 38 weeks, she delivered a healthy baby without neonatal complication. Postpartum day 2, her labs revealed calcium: 10.7mg/dL with albumin: 2.7mg/dL. Discussion: Diagnosis of CY24A1 gene mutation associated hypercalcemia is based on increased 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D ratio and confirmed by genetic analysis. Recommendations are adequate hydration, limiting calcium intake, avoiding vitamin D supplements and preventing sun exposure. It is important to monitor for neonatal hypocalcemia and worsening of maternal hypercalcemia during breastfeeding. We report this case to raise awareness of this rare cause of hypercalcemia in pregnancy and the importance of checking calcium and vitamin D levels prior to vitamin D supplementation. Presentation: Saturday, June 17, 2023