High Prevalence of Kidney Cysts in Patients With CYP24A1 Deficiency

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.

Automated summary

A rare hereditary disease caused by loss-of-function variants in the CYP24A1 gene is characterized by kidney cysts, with a possible association between CYP24A1 deficiency and the formation of these cysts. Retrospective analysis revealed that patients with confirmed or suspected CYP24A1 deficiency exhibited a high prevalence of kidney cysts, suggesting a potential link between CYP24A1 deficiency and cyst development.