A female neonate is found to have ambiguous genitalia at birth: clitoromegaly, posterior labial fusion with a rugated appearance, and a blind vaginal pouch. Karyotype is 46, XX. Serum 17-hydroxyprogesterone is markedly elevated at 48 hours. What is the MOST specific enzyme defect and the immediate life-threatening concern?
- A 11-beta-hydroxylase deficiency; hypertension and hypokalemia
- B 21-hydroxylase deficiency; salt-wasting crisis with hyperkalemia and hyponatremia in the first 2 weeks of life ✓
- C 3-beta-hydroxysteroid dehydrogenase deficiency; partial virilization only
- D 17-alpha-hydroxylase deficiency; hypokalemic hypertension
Explanation
The most common cause of Congenital Adrenal Hyperplasia (CAH) and virilization in a 46,XX neonate is 21-hydroxylase deficiency (~95% of all CAH cases), which blocks conversion of 17-OHP to 11-deoxycortisol (cortisol precursor) and progesterone to deoxycorticosterone (mineralocorticoid precursor). The 17-OHP accumulation is shunted to androgens, causing in utero virilization of the female fetus. In the classic salt-wasting form (~75% of 21-OH deficiency), both cortisol AND aldosterone are deficient, leading to adrenal crisis (hyponatremia, hyperkalemia, dehydration, hypotension, hypoglycemia) typically at 7–14 days of life. Newborn screening and early treatment with hydrocortisone and fludrocortisone are life-saving. 11-beta-hydroxylase deficiency causes virilization + hypertension (excess 11-deoxycorticosterone). 17-alpha-hydroxylase causes male undervirilization and hypertension.
Reference: Ghai Essential Pediatrics, 10th ed.
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