Mitochondrial cytochrome P450 side-chain cleavage enzyme (P450scc) converts cholesterol to pregnenolone and is the initiating enzyme for steroidogenesis. It is encoded by a single-copy gene on chromosome 15. For a long time it was thought that deficiency of P450scc was not compatible with life due to lack of progesterone for maintenance of pregnancy. However, recently a total of 8 patients with missense or even nonsense mutations of CYP11A1 have been described. Depending on the severity of the enzyme dysfunction, patients present with mild to severe early-onset adrenal failure. In 46, XY patients also a disorder of sex development is prevalent with hypospadias to complete female phenotype. P450scc deficiency is the differential diagnosis of congenital lipoid adrenal hyperplasia caused by mutations in the steroidogenic acute regulatory protein, however, in contrast to the latter, these patients do not have adrenal hyperplasia but small adrenals and gonads.