What enzyme deficiency is likely responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol in a newborn with congenital adrenal hyperplasia (CAH) and electrolyte imbalance?

21-Hydroxylase Deficiency in a Newborn with Congenital Adrenal Hyperplasia

The newborn is most likely deficient in 21-hydroxylase (CYP21A2), which is responsible for converting 17-hydroxyprogesterone to 11-deoxycortisol in the cortisol synthesis pathway.

Clinical Presentation Analysis

The clinical presentation strongly indicates congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency:

• Virilization in a female infant: Clitoral enlargement and labioscrotal fusion in a 46,XX karyotype infant 1
• Electrolyte abnormalities: Hypernatremia (151 mg/dL) and hypokalemia (3.2 mg/dL) 1
• Hypertension: Blood pressure of 142/85 mm Hg in a newborn 1

Pathophysiology of 21-Hydroxylase Deficiency

21-hydroxylase deficiency accounts for more than 90% of CAH cases 2. This enzyme deficiency results in:

1. Cortisol synthesis blockade: The enzyme normally converts 17-hydroxyprogesterone to 11-deoxycortisol in the glucocorticoid pathway 3
2. Mineralocorticoid pathway disruption: Also blocks conversion of progesterone to deoxycorticosterone 3
3. Androgen excess: Precursors are diverted to sex hormone biosynthesis, causing virilization 2

Biochemical Confirmation

The biochemical hallmark of 21-hydroxylase deficiency is:

• Elevated 17-hydroxyprogesterone: The substrate accumulates due to the enzyme block 4
• Elevated 21-deoxycortisol: Some accumulated 17-hydroxyprogesterone is converted to 21-deoxycortisol by 11β-hydroxylase, making it a specific marker for 21-hydroxylase deficiency 4, 5

Differential Diagnosis

While the presentation strongly suggests 21-hydroxylase deficiency, other enzyme deficiencies in CAH should be considered:

• 11β-hydroxylase deficiency: Can present with hypertension and hypokalemia but would show elevated 11-deoxycortisol and deoxycorticosterone 1
• 17α-hydroxylase deficiency: Would present with incomplete masculinization in males and primary amenorrhea in females, not virilization 1

Conclusion

The combination of virilization in a female infant with 46,XX karyotype, hypertension, hypernatremia, and hypokalemia is classic for 21-hydroxylase deficiency. This enzyme is critical for converting 17-hydroxyprogesterone to 11-deoxycortisol in the cortisol synthesis pathway, and its deficiency leads to the clinical and biochemical manifestations observed in this newborn.