High Prevalence of Kidney Cysts in Patients With CYP24A1 Deficiency.

Abstract

INTRODUCTION:

Loss-of-function variants in the CYP24A1 gene cause a rare hereditary disease characterized by reduced 24-hydroxylase enzyme activity, increased serum 1,25-dihydroxycholecalciferol levels, hypercalcemia, hypercalciuria, and nephrocalcinosis and/or nephrolithiasis. Kidney cysts in patients with CYP24A1 deficiency were first reported in a single case study from our center. However, a possible association between CYP24A1 deficiency and kidney cysts has not been described.

METHODS:

Retrospective analysis of patients with confirmed or suspected CYP24A1 deficiency and available kidney imaging.

RESULTS:

Among 16 patients with confirmed pathogenic variants, 38% were male and 31% were children, the median age at genetic confirmation was 38 years (range 1-66), and none had a family history of cystic kidney disease. Medullary and/or corticomedullary junction cysts were present in all cases. The median age at first detected cyst was 37 years (range 3-60). The mean and median number of cysts per patient were 5.3 and 2.5 (range 1-37), respectively. Four of 5 further patients with suspected but unconfirmed pathogenic variants had cysts. The number of cysts ≥5 mm in size was above the 97.5th percentile of an age- and sex-matched control population in 55% and 67% of patients with confirmed and suspected pathogenic variants, respectively. At least 1 cyst (≥5 mm in size) was found in 80% of children with confirmed CYP24A1 deficiency.

CONCLUSIONS:

These observations strongly suggest an association between CYP24A1 deficiency and kidney cysts. Further studies are needed to evaluate the role of CYP24A1, vitamin D metabolism, and/or hypercalciuria in cyst formation, and whether cysts exacerbate chronic kidney disease or modify nephrocalcinosis and stone risk.

• Authors: Christian Hanna, Theodora A Potretzke, Andrea G Cogal, Yaman G Mkhaimer, Peter J Tebben, Vicente E Torres, John C Lieske, Peter C Harris, David J Sas, Dawn S Milliner, Fouad T Chebib
• Journal: Kidney international reports (Kidney Int Rep) Vol. 6 Issue 7 Pg. 1895-1903 (Jul 2021) ISSN: 2468-0249 [Electronic] United States
• PMID: 34307984 (Publication Type: Journal Article)
• Copyright: © 2021 International Society of Nephrology. Published by Elsevier Inc.