Genetic disorders of vitamin D biosynthesis

The principal hormonal regulator of bone mineralization is vitamin D, which must be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1 alpha-hydroxylase to yield 1,25 dihydroxy vitamin D. The hormonal regulation of vitamin D activation is at the level of the 1 alpha-hydroxylase. This article reviews the biology of vitamin D, and describes the biochemistry of its activation and the molecular biology of the vitamin D-metabolizing enzymes. Recent advances, principally in the authors' laboratories, have resulted in the cloning of the human vitamin D 1 alpha-hydroxylase and the identification of mutations in its gene that cause Vitamin D Dependent Rickets type I.