A 2-week-old female neonate born to a consanguineous couple presents with salt-wasting crisis: vomiting, poor feeding, hypotension, hyponatremia (Na 118 mEq/L), hyperkalemia (K 7.2 mEq/L), and metabolic acidosis. Genitalia show clitoromegaly and labial fusion. 17-OHP is markedly elevated (>100 nmol/L). Which enzyme deficiency is responsible and what is its mode of inheritance?
- A 11-beta-hydroxylase deficiency; autosomal recessive; presents with hypertension
- B 3-beta-hydroxysteroid dehydrogenase deficiency; autosomal recessive; causes androgen DEFICIENCY in females
- C 21-hydroxylase deficiency; autosomal recessive; accounts for 95% of CAH ✓
- D 17-alpha-hydroxylase deficiency; autosomal recessive; causes 46,XY intersex with hypertension
Explanation
Classical salt-wasting congenital adrenal hyperplasia (CAH) with marked elevation of 17-OHP (precursor to cortisol and androgens), virilization of female genitalia, and adrenal crisis is caused by 21-hydroxylase deficiency, the cause in 90–95% of all CAH cases. This autosomal recessive disorder maps to the CYP21A2 gene on chromosome 6p21. Deficiency of 21-hydroxylase blocks cortisol and aldosterone synthesis, causing ACTH hyperstimulation of the androgens pathway. 11-beta-hydroxylase deficiency also causes virilization but with HYPERTENSION (excess deoxycorticosterone), not salt-wasting. 17-alpha-hydroxylase deficiency causes 46,XY ambiguous genitalia with hypertension and hypokalemia.
Reference: Ghai Essential Pediatrics, 10th ed.
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