THE DELICATE BALANCE OF CYP27B1 AND CYP24A1 IN ENSURING OPTIMAL 1,25-(OH) sub(2)D sub(3) CONCENTRATIONS FOR HUMAN HEALTH

The emergence of human patients with loss-of-function mutations of CYP24A1 and symptoms of hypercalcemia and/or nephrolithiasis and nephrocalcinosis has indicated the critical importance of CYP24A1 in helping to maintain the optimal concentration of 1,25-(OH) sub(2)D sub(3). There have now been over a dozen reports worldwide of individuals with this condition, originally called idiopathic infantile hypercalcemia (IIH), describing both children and adults with this disease and showing that the hypercalcemia can last decades. The answers to questions such as: What causes occasional episodes of hypercalcemia? or How individuals can tolerate such episodes? are important clues to how the delicate balance between CYP27B1 and CYP24A1 is maintained. Furthermore, it would be interesting to know the long-term susceptibility of IIH patients with hypercalcemia to chronic diseases such as cancer, if we could identify and follow such patients worldwide. Recent findings from IIH patients will be discussed.