A 2-week-old female neonate presents with ambiguous genitalia, hyperpigmentation, and on day 7 develops vomiting, poor feeding, and hyponatremia (Na 122 mEq/L) with hyperkalemia (K 6.8 mEq/L). 17-OH progesterone levels are markedly elevated (>300 nmol/L). Which enzyme deficiency is MOST LIKELY and what is the biochemical mechanism for the salt-wasting crisis?
- A 11-beta hydroxylase deficiency; excess 11-deoxycorticosterone causes hypertension but not salt-wasting
- B 21-hydroxylase deficiency; cortisol and aldosterone deficiency leads to salt wasting and excess ACTH drives androgen excess ✓
- C 17-alpha hydroxylase deficiency; inability to produce sex steroids with excess mineralocorticoid causing hypertension
- D 3-beta hydroxysteroid dehydrogenase deficiency; excess DHEA directly causes salt-wasting by antagonizing aldosterone at the renal tubule
Explanation
21-hydroxylase deficiency accounts for >90% of CAH cases. The enzyme converts 17-OH progesterone to 11-deoxycortisol (cortisol pathway) and progesterone to 11-deoxycorticosterone (aldosterone pathway). Deficiency of this enzyme causes: (1) deficient cortisol and aldosterone production causing salt-wasting (hyponatremia, hyperkalemia) and adrenal crisis; (2) ACTH rises due to negative feedback loss, driving excess androgen production (11β-ketotestosterone pathway) causing virilization. The markedly elevated 17-OH progesterone is the biochemical hallmark. 11β-hydroxylase deficiency causes hypertension (due to DOC accumulation), not salt-wasting.
Reference: Ghai Essential Pediatrics, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.