Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes

Abstract

Introduction: Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants. Methods: The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine. Results: The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted cal cium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (50) during follow-up. Conclusions: W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.

Keywords

• vitamin d
• cyp24a1 mutation
• hypercalcaemia
• hypervitaminosis d
• genetic mutation
• phenotype