Testosterone is synthesized from cholesterol in Leydig cells via multiple enzymatic steps. Which enzyme deficiency would cause 46,XY individuals to be phenotypically female with absent Mullerian and Wolffian structures?

• A 5-alpha reductase deficiency — converts testosterone to DHT; affected individuals are phenotypically female at birth
• B StAR (steroidogenic acute regulatory protein) deficiency — cannot transport cholesterol into mitochondria; no steroid hormones including testosterone or AMH produced; Wolffian and Mullerian both regress ✓
• C 17-beta hydroxysteroid dehydrogenase (17β-HSD) deficiency — cannot convert androstenedione to testosterone; no testosterone or AMH is produced
• D Aromatase deficiency — excess testosterone causes virilization of 46,XY individuals

Explanation

StAR deficiency (congenital lipoid adrenal hyperplasia) results in complete inability to transport cholesterol into the mitochondrial inner membrane — the rate-limiting step in all steroid synthesis. Without StAR, no testosterone is made (Wolffian structures regress), and critically, no Anti-Müllerian hormone (AMH, a glycoprotein also requiring cholesterol-derived precursors) is produced — so Müllerian structures also persist (no regression). The phenotype is 46,XY with female external genitalia, blind vagina, absent uterus/fallopian tubes (variable) and absent Wolffian derivatives. 5α-reductase deficiency causes ambiguous genitalia at birth but virilization at puberty (not absent Wolffian structures).

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.