A 2-week-old female neonate presents with ambiguous genitalia: clitoral hypertrophy, posterior labial fusion, and a single urogenital sinus opening. She is found to have a 46,XX karyotype. Serum 17-OH progesterone is markedly elevated at 40,000 ng/dL. Which of the following enzyme deficiency accounts for the MAJORITY of congenital adrenal hyperplasia cases and this clinical presentation?
- A 11-beta hydroxylase deficiency
- B 21-hydroxylase deficiency ✓
- C 3-beta-hydroxysteroid dehydrogenase deficiency
- D 17-alpha hydroxylase deficiency
Explanation
21-hydroxylase deficiency (CYP21A2 mutation) accounts for more than 90-95% of all CAH cases. It impairs conversion of 17-OH progesterone to 11-deoxycortisol (cortisol pathway) and progesterone to 11-deoxycorticosterone (aldosterone pathway), leading to cortisol and aldosterone deficiency with accumulation of 17-OH progesterone and shunting to androgens causing virilization. The classic salt-wasting form (most severe, ~75% of 21-OH deficiency) can present with life-threatening adrenal crisis in the neonate. 11-beta hydroxylase deficiency (~5%) also virilizes 46,XX females but additionally causes hypertension due to excess DOC. Markedly elevated 17-OH progesterone (>10,000 ng/dL) is characteristic of 21-OH deficiency.
Reference: Ghai Essential Pediatrics, 10th ed.
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