Cytochrome P450 oxidoreductase deficiency

Cytochrome P450 oxidoreductase deficiency, abbreviated PORD, is a rare inborn error of metabolism caused by insufficient activity of the enzyme P450 oxidoreductase, or POR. POR is a two-flavin protein responsible for transferring electrons from NADPH to essentially all fifty of the body's microsomal cytochrome P450 enzymes, a large family of enzymes that carry out steroid hormone production, retinoic acid metabolism, and the processing of many drugs; when POR activity is reduced, this whole downstream family of reactions is disrupted rather than any single one. In its severe form the deficiency produces ambiguous genitalia in both male and female infants, congenital adrenal hyperplasia, cortisol deficiency, and a distinctive pattern of skeletal malformation known as Antley-Bixler syndrome; affected pregnancies can also show virilization of the mother, caused by loss of placental aromatase activity that normally protects her from fetal androgens. Milder forms of the deficiency present very differently, showing up as polycystic ovary syndrome in women or hypogonadism in men rather than the dramatic findings of the severe form. Every documented human case is a partial deficiency, since a complete loss of POR activity is understood to be lethal before birth, meaning the disorder is observed only across a spectrum of reduced, never fully absent, enzyme function.