Kidney Week

Abstract: SA-PO258

24 Hydroxylase Deficiency: Comparison with Other Disorders of Vitamin D-Mediated Hypercalcemia

Session Information

• Bone and Mineral Metabolism: Calcium, Magnesium, Kidney Stones
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Azer, Sarah M., Mayo Clinic, Rochester, Minnesota, United States

Sarah M. Azer,

• Vaughan, Lisa E., Mayo Clinic, Rochester, Minnesota, United States

Lisa E. Vaughan,

• Tebben, Peter, Mayo Clinic, Rochester, Minnesota, United States

Peter Tebben,

• Sas, David J., Mayo Clinic, Rochester, Minnesota, United States

David J. Sas,

Background

CYP24A1 gene encodes 24-hydroxylase, an enzyme that converts 25(OH)D₃ (25D) and 1,25(OH)₂D₃ (1,25D) to inactive metabolites. Recent reports establish that loss of function mutations in CYP24A1 are associated with 24 hydroxylase deficiency (24HD), characterized by hypercalcemia, nephrolithiasis, and/or nephrocalcinosis (NC). We retrospectively compared laboratory, imaging, and clinical characteristics of patients with suspected or confirmed 24HD to other disorders of vitamin D-mediated hypercalcemia: sarcoidosis (S), lymphoma (L), and exogenous vitamin D toxicity (EVT).

Methods

Patients seen at Mayo Clinic, Rochester between 1/1/08 and 12/31/16 were further evaluated if they met biochemical criteria: serum calcium ≥9.6 mg/dL, PTH <30 pg/mL, and 1,25D >40 pg/mL. Patients with 24HD were then identified if they met one of the following criteria: 1) positive genetic testing or 2) 25D:24,25D ratio ≥50. Patients with diagnosis of S, L, or EVT were identified by chart review. Patients with fungal infections were also identified but excluded from analysis due to lack of systemic involvement. Data were summarized and reported using median [IQR] for continuous variables and n(%) for categorical variables. Comparisons between disease groups were evaluated using the Fisher exact test for categorical variables and the Wilcoxon rank sum test for continuous variables.

Results

Comparison of 24HD (n=9) to all groups (n=28) revealed 24HD patients were younger at symptom onset (13.75 [1,35] vs 63 [56,79], p=0.001) and more likely to have family history (88.9% vs 20.8%, p<0.001), NC (88.9% vs 6.3%, p<0.001), lower lumbar spine Z-score (-0.50 [-0.80,0.70] vs 1.20 [0.80,2.10], p=0.011), and higher urine Ca:Cr ratio (0.24 [0.21,1.70] vs 0.17 [0.14,0.18], p=0.047).

Conclusion

Patients with 24HD have clinical and laboratory differences compared to other causes of vitamin D mediated hypercalcemia. 24HD should be suspected in hypercalcemic patients who present at a younger age, have a positive family history, and have nephrocalcinosis.

Funding

• Private Foundation Support