title: Successful treatment of hypercalcaemia associated with a CYP24A1 mutation with fluconazole.
abstract: Mutations in CYP24A1, encoding the vitamin D 24-hydroxlase enzyme, are known to cause a range of clinical phenotypes and presentations including idiopathic infantile hypercalcaemia and adult-onset nephrocalcinosis and nephrolithiasis. In the context of raised or borderline high serum calcium levels, suppressed PTH and persistently elevated 1,25 dihydroxy vitamin D levels, this rare condition should be considered. We present a case where this biochemical pattern was seen and mutations in CYP24A1 were confirmed. We were able to successfully control serum calcium levels and reduce urinary calcium excretion by treatment with low-dose fluconazole, which inhibits vitamin D-synthesizing enzymes (including 25-hydroxylases and 1-α-hydroxylase) thereby reducing levels of 1,25-dihydroxy vitamin D.
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Newcastle , UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Sayers
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Newcastle , UK.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Hynes
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Newcastle , UK.
authors.forename: Shalabh
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Newcastle upon Tyne NHS Hospitals Foundation Trust , Newcastle , UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Dowen
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Newcastle , UK ; Newcastle upon Tyne NHS Hospitals Foundation Trust , Newcastle , UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Quinton
authors.affiliation: Newcastle upon Tyne NHS Hospitals Foundation Trust , Newcastle , UK ; Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, NE2 4HH , UK.
authors.forename: Harish K
authors.initials: HK
authors.lastname: Datta
authors.affiliation: Institute of Genetic Medicine , Newcastle University , Newcastle , UK ; Newcastle upon Tyne NHS Hospitals Foundation Trust , Newcastle , UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
keywords: CYP24A1; fluconazole; hypercalcaemia; hypercalciuria; ketoconazole; vitamin D