Question

13 yr old child visit gynaecology OPD with a complaint of not attaining menarche with karyotype 46XX. On examination, clitoromegaly is seen. Which enzyme is most likely to be deficient in the above condition ?

• A. 21 alpha-hydroxylase
• B. 11 beta-hydroxylase
• C. 17 alpha-hydroxylase
• D. 3 beta-hydroxysteroid dehydrogenase

Answer 1

The Correct Option is A

In the scenario described, a 13-year-old child presents with no menarche and clitoromegaly. The karyotype is 46XX, indicating a genetic female. This suggests a condition of Congenital Adrenal Hyperplasia (CAH), which results from enzyme deficiencies affecting adrenal steroidogenesis.

The symptoms of absent menarche and clitoromegaly are indicative of androgen excess. In CAH, the most common enzyme deficiency leading to androgen excess is 21-hydroxylase deficiency.

Here's why 21-hydroxylase deficiency is the likely answer:

• The deficiency in 21-hydroxylase results in impaired cortisol and aldosterone synthesis, leading to an accumulation of steroid precursors.
• These precursors are diverted into the androgen synthesis pathway, resulting in elevated androgens.
• Excess androgens cause virilization, which includes clitoromegaly in genetically female individuals and delayed or absent menarche, as external genitalia may be masculinized.

Other options:

• 11 beta-hydroxylase deficiency also causes virilization but typically presents with hypertension due to the accumulation of deoxycorticosterone.
• 17 alpha-hydroxylase deficiency results in decreased androgen production, which contradicts the symptom of clitoromegaly. It is often associated with hypertension and hypokalemia due to increased mineralocorticoid production.
• 3 beta-hydroxysteroid dehydrogenase deficiency affects glucocorticoid, mineralocorticoid, and androgen synthesis, leading to ambiguous genitalia in both genders but is less common as a cause.

Based on these explanations, the enzyme most likely deficient in this case is 21 alpha-hydroxylase.