A female neonate has ambiguous genitalia (clitoromegaly, posterior labial fusion, urogenital sinus), virilization, and bilateral inguinal masses. Electrolytes show Na+ 124 mEq/L, K+ 6.8 mEq/L, and plasma 17-OH progesterone is markedly elevated (>10,000 ng/dL). Which enzyme deficiency is responsible and which steroid pathway is BLOCKED?
- A 11-beta hydroxylase deficiency — DOCA and androgens accumulate causing hypertension
- B 17-alpha hydroxylase deficiency — cortisol and sex steroids blocked; hypertension from DOCA excess
- C 21-hydroxylase deficiency — cortisol and aldosterone synthesis blocked; androgen precursors accumulate ✓
- D 3-beta hydroxysteroid dehydrogenase deficiency — mild virilization only, no mineralocorticoid defect
Explanation
21-hydroxylase deficiency accounts for ~95% of congenital adrenal hyperplasia (CAH). Deficiency of CYP21A2 blocks conversion of 17-OH progesterone to 11-deoxycortisol (cortisol precursor) and progesterone to deoxycorticosterone (aldosterone precursor), causing: cortisol deficiency (adrenal crisis), aldosterone deficiency (salt-wasting: hyponatremia, hyperkalemia), and androgen excess (excess 17-OH progesterone and androstenedione shunted to androgen synthesis → virilization of female). Markedly elevated 17-OH progesterone is the biochemical hallmark. 11-beta hydroxylase deficiency causes hypertension. 17-alpha hydroxylase causes hypertension and sexual infantilism.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.