A newborn with ambiguous genitalia, mild electrolyte abnormalities (hyponatremia, hyperkalemia), and hyperpigmentation is evaluated. 17-OH progesterone is markedly elevated. The most common enzyme deficiency causing this presentation is:

• A 11β-hydroxylase deficiency
• B 3β-hydroxysteroid dehydrogenase deficiency
• C 17α-hydroxylase deficiency
• D 21-hydroxylase (CYP21A2) deficiency ✓

Explanation

21-hydroxylase (CYP21A2) deficiency accounts for >90% of congenital adrenal hyperplasia (CAH). Deficiency blocks conversion of 17-OH progesterone to 11-deoxycortisol (and progesterone to deoxycorticosterone), causing elevated 17-OH progesterone — the biochemical hallmark. The classic salt-wasting form (most severe) causes aldosterone deficiency (hyponatremia, hyperkalemia, shock) plus cortisol deficiency and virilization from androgen excess. The elevated 17-OH progesterone is shunted to androgen synthesis. Hyperpigmentation results from elevated ACTH (loss of cortisol feedback). 11β-hydroxylase deficiency causes hypertension (DOC accumulation); 17α-hydroxylase causes hypertension with sexual infantilism.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.