Hypercalcemia and CYP24A1 Gene Mutation Diagnosed in the 2nd Trimester of a Twin Pregnancy: A Case Report

Abstract

Patient: Female, 33-year-old Final Diagnosis: Hypercalcemic crisis • pregnancy Symptoms: Hypercalcemia • hypertension • hypertensive crisis • pregnancy Medication: — Clinical Procedure: — Specialty: Genetics Objective: Rare disease Background: Loss-of-function mutations of the CYP24A1 gene cause a deficiency of the CYP24A1 enzyme, which is involved in the catabolism of 1,25-dihydroxyvitamin D3. Patients who are CYP24A1 enzyme deficient are at increased risk of developing hypercalcemia during pregnancy and should avoid additional vitamin D supplementation. This case report provides additional information for managing and diagnosing patients with a CYP24A1 gene mutation. Case Report: A primipara woman with a twin pregnancy was admitted to our hospital for frequent hypertensive crises. She had no history of hypercalcemia-associated signs and symptoms except nephrocalcinosis, and reported no other abnormalities or discomfort at presentation. Laboratory tests revealed that the parathyroid hormone level was suppressed and the serum calcium level was markedly increased. The 25-hydroxyvitamin D level was at the upper limit of the reference range while the 1,25-dihydroxyvitamin D3 level was elevated, suggesting a vitamin D catabolism disorder. A genetic test was performed and a homozygous likely pathogenic variant (based on the American College of Medical Genetics and Genomics guidelines) c.964G>A (p.Glu322Lys) was detected in the CYP24A1 gene (NM_000782.5). A cesarean section delivery was performed due to a single intrauterine demise at 33 weeks of gestation. The preterm newborn was diagnosed with transitional hypercalcemia and hyperphosphatemia; however, he was not treated, as he was asymptomatic. Conclusions: Patients with a CYP24A1 gene mutation are at increased risk of hypercalcemia and fetal demise; therefore, 25-hydroxyvitamin D and calcium levels should be monitored in routine blood tests during pregnancy. Hypercalcemia in a newborn should be carefully evaluated and treated, as hypercalciuria can lead to nephrocalcinosis.

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

“…Conclusions on efficacies of these treatments cannot be made due to the observational nature of these limited data and the challenge to disentangle potential effects of specific drugs (a) from each other when used in combination, (b) from general treatment approaches such as stopping vitamin D supplement intake, and (c) from the natural course of the disease. In general, serum calcium levels were not significantly and consistently reduced or normalized after initiation of the above-described specific drug treatments except for some cases in which vitamin D supplement intake was stopped in parallel (e.g., case numbers 6 and 9 in Table 3) [19,21]. Of note, some authors concluded on the missing effect of their treatment such as in terms of glucocorticoids (case number 13 in Table 3) [24].…”

“…A literature review in PubMed using the search terms "CYP24A1" and "pregnancy" was performed on 13 April 2022 to identify articles presenting data on pregnant women with pathogenic CYP24A1 mutations causing hypercalcemia. Out of 97 articles, we identified 9 eligible manuscripts by this search strategy and by screening their reference lists, we retrieved two additional publications so that 11 articles were included in our work [15][16][17][18][19][20][21][22][23][24][25]. Overall, we retrieved 13 women with pathogenic CYP24A1 mutations who had reports on 29 pregnancies.…”