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Abstract: SA-PO631

A Potential Novel Mutation of CYP24A1 Leading to Hypercalcemia and Hypercalciuria

Session Information

Category: Genetic Diseases of the Kidney

  • 803 Genetic Epidemiology and Other Genetic Studies of Common Kidney Diseases


  • Romney, Pace, University of Utah Medical Center, Salt Lake City, Utah, United States
  • Yenchek, Robert H., None, Salt Lake City, Utah, United States
  • Abraham, Josephine, University of Utah, Holladay, Utah, United States

Mutations of CYP24A1 can lead to a deficiency of vitamin D 24-hydroxylase and can lead to hypercalcemia due to dysregulation of vitamin D 1,25-OH. New mutations are continuing to be discovered.


A 29 year old man with history of prior nephrolithiasis sustained a traumatic pelvic fracture and he was incidentally discovered to have CT findings consistent with severe bilateral medullary nephrocalcinosis, hypercalcemia, and elevated creatinine. Prior to the trauma, the patient was well and had no complaints. He had 24 hour urine collections done and was found to have hypercacliuria. Parathyroid hormone was low, vitamin D 25-OH and vitamin D 1,25-OH levels were both within normal limits. Given his long history of nephrocalcinosis and nephrolithiasis at a young age, a genetic mutation of CYP24A1 was suspected and so he was started on empiric low dose of fluconazole to control his hypercalcemia. He subsequently underwent genetic sequencing for nephrocalcinosis. The results of the genetic test were positive for three mutations; heterozygous for a c.62del (p.Pro21Argfs*8) in CYP24A1, homozygous for c.1219T>A (p.Tyr407Asn) in CYP24A1, and heterozygous for c.374C>G (p.Thr125Arg) in SLC2A9. The heterozygous mutation for CYP24A1 is reported as a recessive mutation for idiopathic infantile hypercalcemia. The heterozygous mutation of SLC2A9 was felt not to fit his clinical picture. The homozygous mutation of CYP24A1 has not been previously reported in literature and modeling predicted this mutation to have probable deleterious effects. Since starting fluconazole, the patient's calcium level has normalized.


Idiopathic hypercalcemia is often caused by genetic mutations of CYP24A1 which encodes for the enzyme 24-hydroxylase. This enzyme promotes the conversion of 25-OHD to 24,25-(OH)2D instead of 1,25-(OH)2D and also promotes the conversion of 1,25-(OH)2D to 1. With a deficiency of this enzyme, various phenotypes of hypercalcemia and nephrocalcinosis have been described. This patient has been found to have a newly discovered mutation of the CYP24A1 gene which is suspected to be causing hypercalcemia and nephrocalcinosis.