Kidney Week

Abstract: PO1527

CYP24A1 Mutations Are Associated with Renal Cystic Disease

Session Information

• Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1001 Genetic Diseases of the Kidneys: Cystic

Authors

• Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Christian Hanna,

• Potretzke, Theodora A., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Theodora A. Potretzke,

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

Peter Tebben,

• Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Vicente E. Torres,

• Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Peter C. Harris,

• Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

John C. Lieske,

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

David J. Sas,

• Milliner, Dawn S., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Dawn S. Milliner,

• Chebib, Fouad T., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fouad T. Chebib,

Background

Loss-of-function mutations in the CYP24A1 gene cause a rare hereditary disease leading to reduced 24-hydroxylase enzyme activity, characterized by increased serum 1,25-dihydroxyvitamin D₃ levels, hypercalcemia, hypercalciuria, nephrocalcinosis, and/or nephrolithiasis. Renal cysts in CYP24A1 mutations were first reported in a single case study from our institution. However, to date a possible association between CYP24A1 mutations and renal cysts has not been examined.

Methods

Retrospective review of all patients with confirmed CYP24A1 mutations and complete renal imaging studies at a tertiary academic center between 2010 and 2020. Cyst location, number, and diameter were measured by contrast-enhanced computed tomography (CT), non-contrast CT, ultrasound or magnetic resonance imaging.

Results

Among the 13 patients with CYP24A1 mutation, 46% were male and 38% children. The mean age at diagnosis was 24.7 ± 18.8 years (range 1-60). Medullary and/or corticomedullary junction renal cysts were present in all 13 cases (5 with unilateral and 8 with bilateral cysts). The mean age at imaging with first detected cyst was 31.1 ± 20.5 years (range 3-61).The median number of cysts per patient was 3 (IQR 1.5-7). The mean size of the smallest and largest cyst were 3.6 ± 2.2 mm (range 2-8) and 11.9 ± 6.9 mm (range 2-30) respectively. All 13 had normal age-adjusted renal size and none had a family history of polycystic kidney disease. The number of cysts (≥ 5 mm in size) in 63% of adult patients was above the 97.5th percentile of an age- and sex-matched control population (Figure 1).

Conclusion

This study suggests an association between CYP24A1 mutations and cystic kidney disease. Further studies are needed to evaluate the role of CYP24A1 and vitamin D metabolism in renal cyst formation, and whether cysts enhance CKD risk in patients with CYP24A1 deficiency, or modify nephrocalcinosis/urinary stone risk.