CYP24A1 gene defect manifesting with gestational hypercalcemia

Area of Science:

• Endocrinology
• Genetics
• Obstetrics

Background:

• Hypercalcemia during pregnancy is uncommon, with primary hyperparathyroidism and PTHrP-producing tumors being frequent causes.
• Less common etiologies include increased calcium absorption, vitamin D intoxication, milk-alkali syndrome, and granulomatous diseases.
• Rarely, gestational hypercalcemia stems from impaired vitamin D catabolism due to CYP24A1 gene mutations.

Observation:

• A 34-year-old patient presented with hypercalcemia, normal intact parathyroid hormone (PTH), and a parathyroid adenoma, successfully treated with surgery.
• Fifteen months post-surgery, she experienced a miscarriage at 8 weeks gestation with borderline high serum calcium.
• At 25 months post-surgery, during a subsequent 12-week pregnancy, she developed symptomatic, PTH-independent hypercalcemia with elevated 1,25(OH)2D levels.

Findings:

• Compound heterozygosity in the CYP24A1 gene was identified as the cause of recurrent hypercalcemia.
• The patient's condition was managed conservatively throughout the pregnancy.
• This represents the first reported case of a CYP24A1 gene defect diagnosed in Hungary.

Implications:

• This case underscores the diagnostic challenges of hypercalcemia in pregnancy.
• It highlights the importance of considering genetic causes like CYP24A1 mutations in recurrent or atypical cases.
• Successful conservative management demonstrates a viable approach for managing such pregnancies.