Vitamin D dependent rickets type I

Vitamin D is present in two forms, ergocalciferol (vitamin D(2)) produced by plants and cholecalciferol (vitamin D(3)) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)(2)D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1α-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1α-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)(2)D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1α-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1α-hydroxylase mutations with clinical findings.