Endocrine Abstracts

Background: CYP24A1 gene encodes the enzyme vitamin D 24-hydroxylase, which converts active vitamin D to inactive metabolites. More than 20 currently described, usually biallelic pathogenic variants of this gene are responsible for idiopathic infantile hypercalcemia manifested typically in childhood (often in newborns) with hypercalcemia, hypercalciuria and nephrocalcinosis. However, a few patients (mostly with monoallelic heterozygous pathogenic variant) can develop mild symptoms – typically intermittent hypercalcemia dependant on vitamin D exposure together with hypercalciuria and nephrocalcinosis - in adulthood.

Case description: We present the case of 43-year old male patient with hypertension and heterozygous Leiden mutation who was sent to endocrinological examination due to hypoparathyroidism, fluctuating hypercalcemia, hypercalciuria and CKDG2A1 caused probably by nephrocalcinosis. Complete laboratory and imaging methods (parameters of calcium-phosphate metabolism, bone scintigraphy and PET-CT) excluded PTH-related peptide-mediated hypercalcemia and granulomatosis. Genetic analysis of gene encoding calcium-sensing receptor did not show any pathogenic variants. Finally, the genetic analysis of CYP24A1 gene revealed the presence of a novel combination of two heterozygous pathogenic variants: CYP24A1: c. 443T>C p.(Leu148Pro) and c.1186C>T p.(Arg396Trp). Unfortunately, the segregation analysis of the proband’s parents in order to confirm trans-heterozygosity (as considered) of the pathogenic variants was not performed due to unwillingness of his parents to undergo the testing.

Conclusion: Differential diagnosis of patients with hypercalciuria, nephrocalcinosis and hypercalcemia related to vitamin D exposure should include CYP24A1 gene mutation. To our knowledge, we were the first to describe this novel combination of two heterozygous pathogenic variants of CYP24A1.