Title: CYP24A1 mutation leading to nephrocalcinosis
Abstract: A 45-year-old man recently came to our attention, who had originally presented with renal colic at the age of 10 years. He subsequently re-presented with a further episode of renal colic and symptomatic hypercalcemia at the age of 45 years, which resulted in an intensive and invasive search for an occult malignancy. A biochemical phenotype of hypercalcemia (serum calcium 2.81mmol/l, serum phosphate 1.15mmol/l), suppressed parathyroid hormone (14ng/l), and hypercalciuria (urinary calcium 8.8mmol/24h) was noted. There was no history of vitamin D supplementation. Total vitamin D levels were normal (117nmol/l). Renal imaging revealed bilateral medullary nephrocalcinosis (Figures 1 and 2). A family history also identified his sister as a renal stone former. His parents had no clinical phenotype. On this basis, an inherited cause of hypercalciuric renal stones seemed much more likely than a malignancy. We confirmed a homozygous E143del mutation, segregating from each parent, who were not known to be consanguineous, in CYP24A1. Although mutations in CYP24A1 may be rare, there is growing evidence that phenotypes of mutations in this gene may include adult presentations of renal stone disease and nephrocalcinosis. A trial of ketoconazole is indicated in order to control the hypercalcemia. Consideration of CYP24A1 mutations as a cause of renal stone disease should be given and a familial pattern of stone formation should be looked for.Figure 2Computed tomography scan showing bilateral nephrocalcinosis.View Large Image Figure ViewerDownload (PPT)