VDR and rickets: Human and animal studies have shown that severe deficiency of vitamin D, as well as inactivating mutations of the genes encoding 1ɑ-hydroxylase (CYP27B1) or the vitamin D receptor (VDR), cause reduced intestinal mineral absorption, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and under-mineralized skeletons (rickets or osteomalacia, depending upon age of onset).1