What condition can cause a male to present with female-appearing ambiguous genitalia?

The condition that can lead a male to present with female-appearing ambiguous genitalia is 21-hydroxylase deficiency, which is one of the most common congenital adrenal hyperplasias. This enzyme deficiency results in impaired cortisol synthesis and leads to an accumulation of steroid precursors, particularly steroid hormones like deoxycorticosterone and 17-hydroxyprogesterone.

In individuals with 21-hydroxylase deficiency, the lack of cortisol synthesis triggers an increase in adrenocorticotropic hormone (ACTH) due to the negative feedback mechanism. This stimulates the adrenal glands to produce excess androgens. If this deficiency occurs in a genetic male (46,XY), the elevated androgen levels can lead to virilization of female external genitalia during fetal development, resulting in ambiguous genitalia at birth.

The specific presentation of ambiguous genitalia, particularly in individuals who are genetically male, is due to the early exposure to excess androgen but the underlying enzymatic defect which hampers the proper development of typical male genitalia can lead to this condition. Additionally, it is important to note that the degree of genital ambiguity can vary depending on the timing and severity of the enzyme block.

In contrast, other forms of enzyme deficiencies such