Late onset presentation of nephrocalcinosis and nephrolithiasis in association with a heterozygous CYP24A1 pathogenic variant.

Abstract

CYP24A1 is gene that encodes one of the cytochrome P450 superfamily enzymes involved in the breakdown of 1,25-dihydroxyvitamin D3. Genetic variants in CYP24A1 lead to a range of phenotypical and biochemical presentations, including idiopathic infantile hypercalcemia, elevated concentrations of 1,25 dihydroxy vitamin D, adult onset nephrocalcinosis, hypercalciuria, hypercalcemia and nephrolithiasis. Here we present an adult female, aged 68 years of age who presented with intermittent abdominal pain, with a past medical history of hypertension. There was a history of oral vitamin D supplementation, however patient denied tanning bed use. There was a family history of kidney stones, with her mother having recurrent kidney stones. Investigations revealed normal serum calcium and total vitamin D levels but evidence of hypercalciuria. Abdominal imaging revealed bilateral nephrocalcinosis. A genetic screen revealed a heterozygous pathogenic variant in CYP24A1. She was managed with stopping vitamin D supplements and encouraging a high fluid intake and initiation of a thiazide diuretic which led to a normalisation of urinary calcium levels. The case exemplifies late onset genetic disease secondary to CYP24A1 loss of function, likely triggered by excessive vitamin D supplementation.