The genetics, pathophysiology, and management of human deficiencies of P450c17

P450c17 commands a central role in human steroidogenesis as the qualitative regulator of steroid hormone flux. Consequently, the study of P450c17 deficiencies in human beings serves to illustrate many aspects of the physiology of steroid biosynthesis and to demonstrate salient features of the genetics and biochemistry of P450c17 itself. Furthermore, classic 17-hydroxylase deficiency was first described in patients with sexual infantilism and hypertension, but it is now recognized that partial and selective forms of P450c17 deficiencies also exist. These patients demonstrate a range of phenotypes, illustrating the multiple roles of P450c17 in human biology. This article reviews the genetics and biochemistry of P450c17 as a prelude for understanding the pathophysiology of these diseases and approaches to their diagnosis and management.