Hereditary Deficiencies in Vitamin D Action

Hereditary deficiencies in vitamin D action can be caused by disturbances in the synthesis of the hormonal form of the vitamin, 1, 25-dihydroxyvitamin D (1, 25(OH)2 D calcitriol), or defects in the interaction of calcitriol and its target tissues. This chapter deals with the hereditary defects in the renal 25-hydroxyvitamin D-1 α–hydroxylase activity. Although rare, the importance of studying hereditary deficiency of vitamin D stems from the fact that they represent a naturally occurring experimental model that helps to elucidate the function and importance of vitamin D and the VDR–effector system in humans in vivo. Hereditary defects along the cascade of 1, 25(OH)2 D synthesis lead to a deficiency in the vitamin D hormonal form. Regarding interaction with the target tissue, calcitriol effects are mediated via a high-affinity intracellular receptor: the vitamin D receptor (VDR). VDR acts as a ligand-modulated transcription factor that belongs to the steroid, thyroid, and retinoic acid receptors gene family. Thus, hereditary defects in the interaction of calcitriol and its target tissues could evolve from defects in hormone binding to VDR, defects in the heterodimerization with RXR or the interaction of the receptor complexes with DNA, or defects in the transcription modulation function.