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.

Keywords: CYP24A1; fluconazole; hypercalcaemia; hypercalciuria; ketoconazole; vitamin D.

Figures

Fig. 1.

Genetic investigations and clinical course of patient. (A) Sequence chromatograms are shown for index case and parents, identifying p.E143del mutation and confirming segregation. (B) Clinical course of patient and response of serum calcium (adjusted for albumin, reference range 2.2–2.6 mmo/L) and 1,25 dihydroxy vitamin D levels (using an validated immunoassay (http://www.idsplc.com/en-gb/products/ids-isys-125-dihydroxy-vitamin-d-is-2400), reference range 20–120 pmol/L) to therapy with variable prednisolone dose (mg) and fluconazole 50 mg od.