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Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1, OH D is impaired as a result of mutations of the 1, OH D-24-hydroxylase cytochrome P450 CYP24A1 Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1, OH D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density.
Of interest, first-time calcium renal stone formers have elevated 1, OH D and evidence of impaired 24-hydroxylase-mediated 1, OH D degradation.J Exp Med. 1934 Feb. 347-79. Medline.
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