Background
CYP24A1 encodes 24-hydroxylase, which converts 25(OH)D3 and 1,25(OH)2D3 to inactive metabolites. Loss-of-function variants in CYP24A1 are associated with 24-hydroxylase deficiency (24HD), characterized by hypercalcemia, nephrolithiasis, and nephrocalcinosis. We retrospectively reviewed laboratory, imaging, and clinical characteristics of patients with suspected or confirmed 24HD and patients with other vitamin D−mediated hypercalcemia disorders: sarcoidosis, lymphoma, and exogenous vitamin-D toxicity (EVT).
Design, setting, participants, & measurements
Patients seen at Mayo Clinic (Rochester, Minnesota) from 1/1/2008-12/31/2016 with the following criteria were retrospectively identified: serum calcium ≥9.6 mg/dL, parathyroid hormone <30 pg/mL, and 1,25(OH)2D3 >40 pg/mL. Patients were considered to have 24HD if they had 1) confirmed CYP24A1 gene variant or 2) 25(OH)D3:24,25(OH)2D ratio ≥50. Patients with sarcoidosis, lymphoma, and EVT were also identified. Groups were compared using the Fisher exact test (categorical variables) or the Wilcoxon rank sum test (continuous variables).
Results
We identified 9 patients with 24HD and 28 with other vitamin D−mediated disorders. Patients with 24HD were younger at symptom onset (median 14 vs 63 years; P=.001) and had positive family history (88.9% vs 20.8%; P<.001), nephrocalcinosis (88.9% vs 6.3%; P<.001), lower lumbar spine Z-scores (median −0.50 vs 1.20; P=.01), higher peak serum phosphorus (% of peak reference range, median 107 vs 84; P=.01), and higher urinary calcium:creatinine ratios (median 0.24 vs 0.17; P=.047).
Conclusion
Patients with 24HD had clinical and laboratory findings that differed from other vitamin D−mediated hypercalcemia disorders. 24HD should be suspected in patients with hypercalcemia who present at younger age, have positive family history, and have nephrocalcinosis.