Which enzyme deficiency is most likely in a newborn with ambiguous external genitalia and electrolyte imbalances?

• A. 21-Hydroxylase deficiency
• B. 17-Hydroxylase deficiency
• C. Cholesterol side-chain cleavage enzyme deficiency
• D. 11-Hydroxylase deficiency

Answer: (A)

The scenario presented involves a newborn with ambiguous external genitalia and electrolyte imbalances, which are key indicators of a specific enzyme deficiency related to steroidogenesis. In this context, 21-hydroxylase deficiency is the most likely cause.

21-hydroxylase plays a crucial role in the adrenal steroid biosynthesis pathway, specifically in the conversion of progesterone to 11-deoxycortisol and 17-hydroxyprogesterone to cortisol. A deficiency in this enzyme leads to decreased cortisol and aldosterone production while causing an accumulation of steroid precursors, such as 17-hydroxyprogesterone. The insufficiency of cortisol prompts increased adrenocorticotropic hormone (ACTH) production, which can lead to adrenal hyperplasia.

The result of the deficiency is a lack of sufficient glucocorticoids and mineralocorticoids, which causes not only electrolyte imbalances, such as hyponatremia and hyperkalemia, due to decreased aldosterone but also the development of ambiguous genitalia due to abnormal androgen levels during critical periods of sexual differentiation in utero.

While other enzyme deficiencies listed can lead to hormonal imbalances and some may also produce ambiguous genitalia, 21-hydroxyl