Loss-of-Function Mutations of <i>CYP24A1</i> , the Vitamin D 24-Hydroxylase Gene, Cause Long-standing Hypercalciuric Nephrolithiasis and Nephrocalcinosis

Abstract

Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, cause severe hypercalciuric nephrolithiasis and nephrocalcinosis. The mutations may present in adults and may lead to chronic renal insufficiency. Our results support a recessive mode of inheritance. CYP24A1 mutations should be considered in the differential diagnosis of hypercalciuric nephrolithiasis, especially as many adults are now prescribed supplemental oral vitamin D.