VDDR-II is caused by mutations in which receptor?

• A. PTH receptor
• B. Calcitonin receptor
• C. Vitamin D binding protein
• D. Vitamin D receptor

Answer: (D)

Mutations in the vitamin D receptor disrupt the body's ability to respond to the active form of vitamin D, calcitriol. This receptor is a nuclear transcription factor that, when activated by calcitriol, turns on genes that promote calcium and phosphate absorption in the gut and proper mineralization in bone. If the receptor is defective, target tissues don’t respond to calcitriol even though levels may be high, leading to vitamin D–resistant rickets with hypocalcemia or inappropriately normal calcium, hypophosphatemia, secondary hyperparathyroidism, and often alopecia. This specific receptor-level defect explains why rickets persists despite sufficient or elevated vitamin D activity.

Other options involve different proteins or receptors: a PTH receptor mutation causes a different form of resistance (pseudohypoparathyroidism); a deficiency of the vitamin D binding protein would mostly reduce circulating vitamin D transport rather than signaling; a calcitonin receptor mutation would affect calcitonin signaling rather than the vitamin D pathway.