Treatment of Rickets in Vitamin D-Dependent Rickets Type 1B (CYP2R1 Mutation, Impaired 25-Hydroxylation)

This protocol applies to patients with vitamin D-dependent rickets type 1B (VDDR1B), a rare genetic disorder caused by mutations in the CYP2R1 gene. These mutations result in impaired 25-hydroxylation of vitamin D, meaning the conversion of vitamin D2 and vitamin D3 to 25(OH)D — the key circulating intermediate — is defective, leading to inadequate 25(OH)D concentrations despite vitamin D intake.

Because the enzymatic defect lies specifically at the 25-hydroxylation step, management centres on a form of vitamin D that bypasses this impaired conversion, combined with calcium supplementation. Alternative vitamin D formulations may also be considered. The complete regimen — including drug selection, sequencing, and monitoring parameters — is detailed in the full protocol.