Abstract: SA-PO0573
Single-Center Experience with CYP24A1 Variants in Adults with Nephrolithiasis
Session Information
- Bones, Stones, and Mineral Metabolism: Research and Cases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Dupont, Julian Henri, Geisinger Medical Center, Danville, Pennsylvania, United States
- Al Khateeb, Mohammad Husni Sadeq, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, Pennsylvania, United States
- Bucaloiu, Ion D., Geisinger Medical Center, Danville, Pennsylvania, United States
- Chang, Alexander R., Geisinger Medical Center, Danville, Pennsylvania, United States
- Green, Jamie Alton, Geisinger Medical Center, Danville, Pennsylvania, United States
Background
Variants in the CYP24A1 gene encoding 24-hydroxylase disrupt vitamin D metabolism cause hypercalcemic and renal phenotypes. Homozygous loss-of-function mutations in CYP24A1 encoding 24-hydroxylase lead to excess calcitriol (1,25-OH D), increased intestinal calcium absorption and idiopathic infantile hypercalcemia. In adults the phenotype is variable and includes hyperabsorbtive hypercalciuria, nephrolithiasis, nephrocalcinosis, and episodic hypercalcemia often triggered by vitamin D exposure or pregnancy. Treatment includes azoles, which inhibit calcitriol synthesis via 1-alpha hydroxylase blockade, or rifampin, which induces alternative calcitriol degradation through CYP3A4.
Methods
Six patients, 83% female, from 4 families, with pathogenic or likely pathogenic CYP24A1 variants including 3 homozygous, 1 compound heterozygous and 2 heterozygous, were evaluated in the Geisinger kidney stone clinic. Data from electronic health record review is summarized below.
Results
All patients had baseline hypercalciuria and nephrolithiasis. Untreated peak 24-hour urine calcium ranged 229 to 668 mg/day. Two related homozygous women had severe pregnancy-associated hypercalcemia, with peak serum calcium up to 17.1 mg/dL. This is likely due to physiologic increase in conversion of 25-OH D to 1,25-OH D during pregnancy and lactation. One homozygous female was treated with fluconazole alone, and two others, one homozygous and one heterozygous female, with fluconazole plus thiazide, and they had marked reductions in urinary calcium. Two patients were treated with thiazide alone. One heterozygous female with severe hypercalciuria but no radiographic stone disease did not receive stone-preventive therapy.
Conclusion
The phenotypic spectrum of patients with CYP24A1 variants is broad. In select patients with high calcitriol and hypercalciuria, combined azole and thiazide therapy appears effective in reducing urinary calcium and NL risk. Larger studies are needed to define genotype-phenotype correlations and clarify optimal treatments.