Analysis of vitamin D3 metabolites in survivors of infantile idiopathic hypercalcemia caused by CYP24A1 mutation or SLC34A1 mutation

Infantile hypercalcemia (IH), is a rare disorder caused by CYP24A1 or SLC34A1 variants which lead to disturbed catabolism of 25(OH)D3 and 125(OH)2D3 or increased generation of 125(OH)2D3. Aim of study To assess the status of 2425(OH)2D3 and other markers of vitamin D in IH survivors, in whom variants of CYP24A1 or SLC34A1 gene were found and to compare these unique biochemical features with those obtained from subjects who were diagnosed in the first year of life with hypercalcemia, elevated 25(OH)D3 and low PTH but in whom neither CYP24A1 nor SLC34A1 variant was found. Patients and methods 16 IH survivors in whom CYP24A1 (n = 13) or SLC34A1 (n = 3) variants were found and 41 subjects in whom hypercalcemia was diagnosed in the first year of life but in whom CYP24A1 or SLC34A1 variants were not found were included in the study. 25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, 2425(OH)2D3 were assessed by liquid chromatography coupled with tandem mass spectrometry. 125(OH)2D3 concentrations were assessed by chemiluminescence. Results Subjects with CYP24A1 variants, despite normal 25(OH)D3 levels, had higher 25(OH)D3/2425(OH)2D3 ratio values (487; 265−1073 ng/mL) when compared to subjects with SLC34A1 variants (16; 16−23 ng/mL) and with subjects in whom CYP24A1 or SLC34A1 were not found (56; 9−56 ng/mL) (p = 0.00003). Separation of interfering metabolite further increased differences between subjects with and without CYP24A1 mutation. Conclusions Survivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D3/2425(OH)2D3 ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.