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24-hydroxylase deficiency: comparison with other disorders of vitamin D-mediated hypercalcemia
Category: Bone and Mineral Metabolism
Authors: Sarah M. Azer, Mayo Clinic; Lisa E. Vaughan, MS; Peter Tebben, MD; David J. Sas DO, MPH
This study compared laboratory, imaging, clinical characteristics of patients with suspected or confirmed 24 Hydroxylase (24HD) “to other disorders of vitamin D-mediated hypercalcemia such as, sarcoidosis (S), lymphoma (L), and exogenous vitamin D toxicity (EVT).” Patients with 24 Hydroxylase (24HD) “have clinical and laboratory differences compared to other causes of vitamin D mediated hypercalcemia.” For patients with hypercalcemia who present at a young age, have a positive family history, and have nephrocalcinosis, clinicians should suspect 24HD.
At Mayo Clinic in Rochester, New York, between January 1, 2008 and December 31, 2016, current patients, who had been going there regularly, “were further evaluated if they met a certain biochemical criteria characterized by: serum calcium ≥9.6 mg/dL, PTH <30 pg/mL, and 1,25D>40 pg/mL.” If patients met one of the following, either a positive genetic testing or 25D:24,25D ratio ≥50, they were identified with 24HD.
More identifications included:
- A diagnosis of S, L, or EVT by chart review
- Patients with fungal diseases (these patients were excluded, however, due to “lack of system involvement”)
Using the “Fisher exact test for categorical variable and the Wilcoxon rank sum test for continues variables”, comparisons showed that 24HD patients were younger at symptom onset (13.5 vs. 63) and were more likely to have a family history, NC, lower lumbar spine Z-score and a higher urine Ca:Cr ratio.
“CYP24A1 gene encodes 24HD, an enzyme that converts 25(OH)D3 and 1,25(OH)2D3 to inactive metabolites.” According to recent reports, loss of function mutations in CYP24A1 are associated with 24HD deficiency that is characterized by hypercalcemia, nephrolithiasis, and/or nephrocalcinosis.