The Pathophysiology and Genetics of Congenital Lipoid Adrenal Hyperplasia

Patients with congenital lipoid adrenal hyperplasia, the most severe genetic disorder of steroid hormone biosynthesis, have a severe defect in the conversion of cholesterol to pregnenolone, the first step in adrenal and gonadal steroidogenesis. Deficient fetal testicular steroidogenesis in patients with a 46,XY karyotype results in phenotypically normal female genitalia. The adrenal cortex becomes engorged with cholesterol and cholesterol esters; deficient adrenal steroidogenesis leads to salt wasting, hyponatremia, hypovolemia, hyperkalemia, acidosis, and death in infancy, 1 , 2 although patients can survive to adulthood with appropriate mineralocorticoid- and glucocorticoid-replacement therapy. 3 , 4 Some affected infants have immediate signs of mineralocorticoid deficiency, but others . . .